419
Views
1
CrossRef citations to date
0
Altmetric
REVIEW

Field-Deployable Treatments For Leishmaniasis: Intrinsic Challenges, Recent Developments and Next Steps

ORCID Icon, , , ORCID Icon, , & show all
Pages 61-85 | Received 01 Mar 2023, Accepted 08 Jun 2023, Published online: 20 Jul 2023

References

  • CDC. DPDx – Leishmaniasis:23. Available from: https://www.cdc.gov/dpdx/leishmaniasis/index.html. Accessed June 8, 2023.
  • David CV, Craft N. Cutaneous and mucocutaneous leishmaniasis. Dermatol Ther. 2009;22(6):491. doi:10.1111/j.1529-8019.2009.01272.x
  • Reithinger R, Dujardin JC, Louzir H, Pirmez C, Alexander B, Brooker S. Cutaneous leishmaniasis. Lancet Infect Dis. 2007;7(9):581–596. doi:10.1016/S1473-3099(07)70209-8
  • Burza S, Croft SL, Boelaert M. Leishmaniasis. Lancet. 2018;392(10151):951–970. doi:10.1016/S0140-6736(18)31204-2
  • Alcantara LM, Ferreira TCS, Gadelha FR, Miguel DC. Challenges in drug discovery targeting TriTryp diseases with an emphasis on leishmaniasis. Int J Parasitol Drugs Drug Resist. 2018;8(3):430–439. doi:10.1016/j.ijpddr.2018.09.006
  • Tiuman TS, Santos AO, Ueda-Nakamura T, Filho BP, Nakamura CV. Recent advances in leishmaniasis treatment. Int J Infect Dis. 2011;15(8):e525–32. doi:10.1016/j.ijid.2011.03.021
  • McGwire BS, Satoskar AR. Leishmaniasis: clinical syndromes and treatment. QJM. 2014;107(1):7–14. doi:10.1093/qjmed/hct116
  • Varma N, Naseem S. Hematologic changes in visceral leishmaniasis/kala azar. Indian J Hematol Blood Transfus. 2010;26(3):78. doi:10.1007/s12288-010-0027-1
  • Zijlstra EE. The immunology of post-kala-azar dermal leishmaniasis (PKDL). Parasit Vectors. 2016;9:464. doi:10.1186/s13071-016-1721-0
  • Lypaczewski P, Matlashewski G. Leishmania donovani hybridisation and introgression in nature: a comparative genomic investigation. Lancet Microbe. 2021;2(6):e250–e258. doi:10.1016/S2666-5247(21)00028-8
  • Adaui V, Lye LF, Akopyants NS, et al. Association of the endobiont double-stranded RNA virus LRV1 with treatment failure for human leishmaniasis caused by leishmania braziliensis in Peru and Bolivia. J Infect Dis. 2016;213(1):112–121. doi:10.1093/infdis/jiv354
  • Kuhlmann FM, Robinson JI, Bluemling GR, Ronet C, Fasel N, Beverley SM. Antiviral screening identifies adenosine analogs targeting the endogenous dsRNA Leishmania RNA virus 1 (LRV1) pathogenicity factor. Proc Natl Acad Sci U S A. 2017;114(5):E811–E819. doi:10.1073/pnas.1619114114
  • Hartley MA, Ronet C, Zangger H, Beverley SM, Fasel N. Leishmania RNA virus: when the host pays the toll. Front Cell Infect Microbiol. 2012;2:99. doi:10.3389/fcimb.2012.00099
  • Uliana SRB, Trinconi CT, Coelho AC. Chemotherapy of leishmaniasis: present challenges. Parasitology. 2018;145(4):464–480. doi:10.1017/S0031182016002523
  • Moore EM, Lockwood DN. Treatment of visceral leishmaniasis. J Glob Infect Dis. 2010;2(2):151–158. doi:10.4103/0974-777X.62883
  • Ponte-Sucre A, Gamarro F, Dujardin JC, et al. Drug resistance and treatment failure in leishmaniasis: a 21st century challenge. PLoS Negl Trop Dis. 2017;11(12):e0006052. doi:10.1371/journal.pntd.0006052
  • Madusanka RK, Silva H, Karunaweera ND. Treatment of cutaneous leishmaniasis and insights into species-specific responses: a narrative review. Infect Dis Ther. 2022;11(2):695–711. doi:10.1007/s40121-022-00602-2
  • Alrajhi AA, Ibrahim EA, De Vol EB, Khairat M, Faris RM, Maguire JH. Fluconazole for the treatment of cutaneous leishmaniasis caused by Leishmania major. N Engl J Med. 2002;346(12):891–895. doi:10.1056/NEJMoa011882
  • Galvao EL, Rabello A, Cota GF. Efficacy of azole therapy for tegumentary leishmaniasis: a systematic review and meta-analysis. PLoS One. 2017;12(10):e0186117. doi:10.1371/journal.pone.0186117
  • Saenz RE, Paz H, Berman JD. Efficacy of ketoconazole against Leishmania braziliensis panamensis cutaneous leishmaniasis. Am J Med. 1990;89(2):147–155. doi:10.1016/0002-9343(90)90292-l
  • Ballou WR, McClain JB, Gordon DM, et al. Safety and efficacy of high-dose sodium stibogluconate therapy of American cutaneous leishmaniasis. Lancet. 1987;2(8549):13–16. doi:10.1016/s0140-6736(87)93053-4
  • Sundar S, Chakravarty J. Liposomal amphotericin B and leishmaniasis: dose and response. J Glob Infect Dis. 2010;2(2):159–166. doi:10.4103/0974-777X.62886
  • Gadelha EPN, Ramasawmy R, da Costa Oliveira B, et al. An open label randomized clinical trial comparing the safety and effectiveness of one, two or three weekly pentamidine isethionate doses (seven milligrams per kilogram) in the treatment of cutaneous leishmaniasis in the Amazon Region. PLoS Negl Trop Dis. 2018;12(10):e0006850. doi:10.1371/journal.pntd.0006850
  • Krause G, Kroeger A. Topical treatment of American cutaneous leishmaniasis with paramomycin and methylbenzethonium chloride: a clinical study under field conditions in Ecuador. Trans R Soc Trop Med Hyg. 1994;88(1):92–94. doi:10.1016/0035-9203(94)90517-7
  • Soto J, Grogl M, Berman J, Olliaro P. Limited efficacy of injectable aminosidine as single-agent therapy for Colombian cutaneous leishmaniasis. Trans R Soc Trop Med Hyg. 1994;88(6):695–698. doi:10.1016/0035-9203(94)90235-6
  • Zerpa O, Ulrich M, Blanco B, et al. Diffuse cutaneous leishmaniasis responds to miltefosine but then relapses. Br J Dermatol. 2007;156(6):1328–1335. doi:10.1111/j.1365-2133.2007.07872.x
  • Wolf Nassif P, De Mello TF, Navasconi TR, et al. Safety and efficacy of current alternatives in the topical treatment of cutaneous leishmaniasis: a systematic review. Parasitology. 2017;144(8):995–1004. doi:10.1017/S0031182017000385
  • Khamesipour A. Therapeutic vaccines for leishmaniasis. Expert Opin Biol Ther. 2014;14(11):1641–1649. doi:10.1517/14712598.2014.945415
  • Husein-ElAhmed H, Gieler U, Steinhoff M. Evidence supporting the enhanced efficacy of pentavalent antimonials with adjuvant therapy for cutaneous leishmaniasis: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2020;34(10):2216–2228. doi:10.1111/jdv.16333
  • Berbert TRN, de Mello TFP, Wolf Nassif P, et al. Pentavalent antimonials combined with other therapeutic alternatives for the treatment of cutaneous and mucocutaneous leishmaniasis: a systematic review. Dermatol Res Pract. 2018;2018:1–21. doi:10.1155/2018/9014726
  • Garza-Tovar TF, Sacriste-Hernandez MI, Juarez-Duran ER, Arenas R. An overview of the treatment of cutaneous leishmaniasis. Fac Rev. 2020;9:28. doi:10.12703/r/9-28
  • Velasco-Castrejon O, Walton BC, Rivas-Sanchez B, et al. Treatment of cutaneous leishmaniasis with localized current field (radio frequency) in Tabasco, Mexico. Am J Trop Med Hyg. 1997;57(3):309–312. doi:10.4269/ajtmh.1997.57.309
  • Aronson NE, Wortmann GW, Byrne WR, et al. A randomized controlled trial of local heat therapy versus intravenous sodium stibogluconate for the treatment of cutaneous Leishmania major infection. PLoS Negl Trop Dis. 2010;4(3):e628. doi:10.1371/journal.pntd.0000628
  • Volpedo G, Huston RH, Holcomb EA, et al. From infection to vaccination: reviewing the global burden, history of vaccine development, and recurring challenges in global leishmaniasis protection. Expert Rev Vaccines. 2021;20(11):1431. doi:10.1080/14760584.2021.1969231
  • Panagiotopoulos A, Stavropoulos PG, Hasapi V, Papakonstantinou AM, Petridis A, Katsambas A. Treatment of cutaneous leishmaniasis with cryosurgery. Int J Dermatol. 2005;44(9):749–752. doi:10.1111/j.1365-4632.2005.02628.x
  • Al-Qubati Y, Janniger EJ, Schwartz RA. Cutaneous leishmaniasis: cryosurgery using carbon dioxide slush in a resource-poor country. Int J Dermatol. 2012;51(10):1217–1220. doi:10.1111/j.1365-4632.2011.04958.x
  • Lopez-Carvajal L, Cardona-Arias JA, Zapata-Cardona MI, Sanchez-Giraldo V, Velez ID. Efficacy of cryotherapy for the treatment of cutaneous leishmaniasis: meta-analyses of clinical trials. BMC Infect Dis. 2016;16:360. doi:10.1186/s12879-016-1663-3
  • Aronson N, Herwaldt BL, Libman M, et al. Diagnosis and treatment of leishmaniasis: clinical practice guidelines by the infectious diseases society of America (IDSA) and the American society of tropical medicine and hygiene (ASTMH). Clin Infect Dis. 2016;63(12):1539. doi:10.1093/cid/ciw742
  • Pinheiro AC, de Souza MVN. Current leishmaniasis drug discovery. RSC Med Chem. 2022;13(9):1029. doi:10.1039/d1md00362c
  • Thompson AM, O’Connor PD, Marshall AJ, et al. 7-substituted 2-Nitro-5,6-dihydroimidazo 2,1-b 1,3 oxazines: novel antitubercular agents lead to a new preclinical candidate for visceral leishmaniasis. J Med Chem. 2017;60(10):4212. doi:10.1021/acs.jmedchem.7b00034
  • Van den Kerkhof M, Leprohon P, Mabille D, et al. Identification of resistance determinants for a promising antileishmanial oxaborole series. Microorganisms. 2021;9(7):1408. doi:10.3390/microorganisms9071408
  • Machado-Pinto J, Pinto J, da Costa CA, et al. Immunochemotherapy for cutaneous leishmaniasis: a controlled trial using killed Leishmania (Leishmania) amazonensis vaccine plus antimonial. Int J Dermatol. 2002;41(2):73–78. doi:10.1046/j.1365-4362.2002.01336.x
  • Mayrink W, Botelho AC, Magalhaes PA, et al. Immunotherapy, immunochemotherapy and chemotherapy for American cutaneous leishmaniasis treatment. Rev Soc Bras Med Trop. 2006;39(1):14–21. doi:10.1590/s0037-86822006000100003
  • Convit J, Ulrich M, Zerpa O, et al. Immunotherapy of American cutaneous leishmaniasis in Venezuela during the period 1990–99. Trans R Soc Trop Med Hyg. 2003;97(4):469–472. doi:10.1016/s0035-9203(03)90093-9
  • Datta A, Podder I, Das A, Sil A, Das NK. Therapeutic modalities in post kala-azar dermal leishmaniasis: a systematic review of the effectiveness and safety of the treatment options. Indian J Dermatol. 2021;66(1):34–43. doi:10.4103/ijd.IJD_264_20
  • Taslimi Y, Zahedifard F, Rafati S. Leishmaniasis and various immunotherapeutic approaches. Parasitology. 2018;145(4):497–507. doi:10.1017/S003118201600216X
  • Moafi M, Rezvan H, Sherkat R, Taleban R. Leishmania vaccines entered in clinical trials: a review of literature. Int J Prev Med. 2019;10:95. doi:10.4103/ijpvm.IJPVM_116_18
  • Shaddel M, Sharifi I, Karvar M, Keyhani A, Baziar Z. Cryotherapy of cutaneous leishmaniasis caused by Leishmania major in BALB/c mice: a comparative experimental study. J Vector Borne Dis. 2018;55(1):42–46. doi:10.4103/0972-9062.234625
  • Gedda MR, Singh B, Kumar D, et al. Post kala-azar dermal leishmaniasis: a threat to elimination program. PLoS Negl Trop Dis. 2020;14(7):e0008221. doi:10.1371/journal.pntd.0008221
  • Mansueto P, Seidita A, Vitale G, Cascio A. Transfusion transmitted leishmaniasis. What to do with blood donors from endemic areas? Travel Med Infect Dis. 2014;12(6 Pt A):617–627. doi:10.1016/j.tmaid.2014.10.011
  • Mirzabeigi M, Farooq U, Baraniak S, Dowdy L, Ciancio G, Vincek V. Reactivation of dormant cutaneous Leishmania infection in a kidney transplant patient. J Cutan Pathol. 2006;33(10):701–704. doi:10.1111/j.1600-0560.2006.00532.x
  • Antinori S, Cascio A, Parravicini C, Bianchi R, Corbellino M. Leishmaniasis among organ transplant recipients. Lancet Infect Dis. 2008;8(3):191–199. doi:10.1016/S1473-3099(08)70043-4
  • Peris MP, Esteban-Gil A, Ares-Gómez S, Morales M, Castillo JA, Moreno B. Characterization of lesions in the temporal muscle and the male reproductive system (epididymis and testicle) of dogs experimentally infected with Leishmania infantum with different clinical stages. Vet Parasitol. 2022;305. doi:10.1016/j.vetpar.2022.109700
  • Boechat VC, Pereira SA, Júnior AAVM, et al. Frequency, active infection and load of Leishmania infantum and associated histological alterations in the genital tract of male and female dogs. PLoS One. 2020;15(9):e0238188. doi:10.1371/journal.pone.0238188
  • Boechat VC, Mendes Junior AAV, Madeira M, et al. Occurrence of Leishmania infantum and associated histological alterations in the genital tract and mammary glands of naturally infected dogs. Parasitol Res. 2016;115(6):2371. doi:10.1007/s00436-016-4987-4
  • Turchetti AP, Souza TD, Paixão TA, Santos RL. Sexual and vertical transmission of visceral leishmaniasis. J Infect Dev Ctries. 2014;8(4):403. doi:10.3855/jidc.4108
  • Mignot G, Bhattacharya Y, Reddy A. Ocular Leishmaniasis - A systematic review. Indian J Ophthalmol. 2021;69(5):1052. doi:10.4103/ijo.IJO_2232_20
  • Maia CSF, Monteiro MC, Gavioli EC, Oliveira FR, Oliveira GB, Romão PRT. Neurological disease in human and canine leishmaniasis--clinical features and immunopathogenesis. Parasite Immunol. 2015;37(8):385. doi:10.1111/pim.12203
  • Petersen CA, Greenlee MHW. Neurologic manifestations of Leishmania spp. infection. J Neuroparasitology. 2011;2:1–5. doi:10.4303/jnp/N110401
  • Llanos-Cuentas A, Valencia BM, Petersen CA. Neurological manifestations of human leishmaniasis. Handb Clin Neurol. 2013;114:193. doi:10.1016/b978-0-444-53490-3.00013-3
  • Sbrana S, Marchetti V, Mancianti F, Guidi G, Bennett D. Retrospective study of 14 cases of canine arthritis secondary to Leishmania infection. J Small Anim Pract. 2014;55(6):309. doi:10.1111/jsap.12204
  • Guidelli GM, De Stefano R, Galeazzi M, Selvi E. Synovial Leishmaniasis. Arthritis Rheumatol. 2016;68(4):931. doi:10.1002/art.39541
  • Mehrotra R, Choudhry VP, Saxena R, Kapila K, Saraya AK. Asymptomatic visceral leishmaniasis in a child with acute lymphoblastic leukaemia. J Infect. 1995;30(2):157. doi:10.1016/s0163-4453(95)80012-3
  • Grinnage-Pulley T, Scott B, Petersen CA. A mother’s gift: congenital transmission of trypanosoma and leishmania species. PLoS Pathog. 2016;12(1):e1005302. doi:10.1371/journal.ppat.1005302
  • Berger BA, Bartlett AH, Saravia NG, Galindo Sevilla N. Pathophysiology of leishmania infection during pregnancy. Trends Parasitol. 2017;33(12):935. doi:10.1016/j.pt.2017.08.012
  • Figueiró-Filho EA, Duarte G, El-Beitune P, Quintana SM, Maia TL. Visceral leishmaniasis (kala-azar) and pregnancy. Infect Dis Obstet Gynecol. 2004;12(1):31. doi:10.1080/1064744042000210384
  • Pagliano P, Carannante N, Rossi M, et al. Visceral leishmaniasis in pregnancy: a case series and a systematic review of the literature. J Antimicrob Chemother. 2005;55(2):229. doi:10.1093/jac/dkh538
  • Gajurel K, Dhakal R, Deresinski S. Leishmaniasis in solid organ and hematopoietic stem cell transplant recipients. Clin Transplant. 2017;31(1):e12867. doi:10.1111/ctr.12867
  • Tatarelli P, Fornaro G, Del Bono V, et al. Visceral leishmaniasis in hematopoietic cell transplantation: case report and review of the literature. J Infect Chemother. 2018;24(12):990. doi:10.1016/j.jiac.2018.05.008
  • Makoni M. New threats to visceral leishmaniasis control. Lancet Microbe. 2021;2(11):e574. doi:10.1016/S2666-5247(21)00285-8
  • Mesa-Arango AC, Scorzoni L, Zaragoza O. It only takes one to do many jobs: amphotericin B as antifungal and immunomodulatory drug. Front Microbiol. 2012;3:286. doi:10.3389/fmicb.2012.00286
  • Shafiei M, Peyton L, Hashemzadeh M, Foroumadi A. History of the development of antifungal azoles: a review on structures, SAR, and mechanism of action. Bioorg Chem. 2020;104:104240. doi:10.1016/j.bioorg.2020.104240
  • Cohen BE, Gamargo M. Concentration and time dependence of amphotericin B-induced permeability changes across plasma membrane vesicles from Leishmania sp. Drugs Exp Clin Res. 1987;13(9):539–546.
  • Ramos H, Valdivieso E, Gamargo M, Dagger F, Cohen BE. Amphotericin B kills unicellular leishmanias by forming aqueous pores permeable to small cations and anions. J Membr Biol. 1996;152(1):65–75. doi:10.1007/s002329900086
  • Keighobadi M, Emami S, Fakhar M, Shokri A, Mirzaei H, Hosseini Teshnizi S. Repurposing azole antifungals into antileishmanials: novel 3-triazolylflavanones with promising in vitro antileishmanial activity against Leishmania major. Parasitol Int. 2019;69:103–109. doi:10.1016/j.parint.2018.12.006
  • Leonard R, Hardy J, van Tienhoven G, et al. Randomized, double-blind, placebo-controlled, multicenter trial of 6% miltefosine solution, a topical chemotherapy in cutaneous metastases from breast cancer. J Clin Oncol. 2001;19(21):4150–4159. doi:10.1200/JCO.2001.19.21.4150
  • Dorlo TP, Balasegaram M, Beijnen JH, de Vries PJ. Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. J Antimicrob Chemother. 2012;67(11):2576–2597. doi:10.1093/jac/dks275
  • Van Bocxlaer K, Yardley V, Murdan S, Croft SL. Topical formulations of miltefosine for cutaneous leishmaniasis in a BALB/c mouse model. J Pharm Pharmacol. 2016;68(7):862–872. doi:10.1111/jphp.12548
  • Bustamante C, Ochoa R, Asela C, Muskus C. Repurposing of known drugs for leishmaniasis treatment using bioinformatic predictions, in vitro validations and pharmacokinetic simulations. J Comput Aided Mol Des. 2019;33(9):845–854. doi:10.1007/s10822-019-00230-y
  • Carvalho-Gontijo R, Moreira DR, Resende M, et al. Infection of hematopoietic stem cells by Leishmania infantum increases erythropoiesis and alters the phenotypic and functional profiles of progeny. Cell Immunol. 2018;326:77. doi:10.1016/j.cellimm.2017.10.016
  • Challen GA, Boles N, Lin KK, Goodell MA. Mouse hematopoietic stem cell identification and analysis. Cytometry A. 2009;75(1):14–24. doi:10.1002/cyto.a.20674
  • Pinto AI, Brown N, Preham O, Doehl JSP, Ashwin H, Kaye PM. TNF signalling drives expansion of bone marrow CD4+ T cells responsible for HSC exhaustion in experimental visceral leishmaniasis. PLoS Pathog. 2017;13(7):e1006465. doi:10.1371/journal.ppat.1006465
  • Abidin BM, Hammami A, Stager S, Heinonen KM. Infection-adapted emergency hematopoiesis promotes visceral leishmaniasis. PLoS Pathog. 2017;13(8):e1006422. doi:10.1371/journal.ppat.1006422
  • Kumar P, Misra P, Thakur CP, Saurabh A, Rishi N, Mitra DK. T cell suppression in the bone marrow of visceral leishmaniasis patients: impact of parasite load. Clin Exp Immunol. 2018;191(3):318–327. doi:10.1111/cei.13074
  • Kima PE, Soong L. Interferon gamma in leishmaniasis. Front Immunol. 2013;4:156. doi:10.3389/fimmu.2013.00156
  • Rai AK, Thakur CP, Singh A, et al. Regulatory T cells suppress T cell activation at the pathologic site of human visceral leishmaniasis. PLoS One. 2012;7(2):e31551. doi:10.1371/journal.pone.0031551
  • Murray HW. Clinical and experimental advances in treatment of visceral leishmaniasis. Antimicrob Agents Chemother. 2001;45(8):2185–2197. doi:10.1128/AAC.45.8.2185-2197.2001
  • Saha S, Mondal S, Ravindran R, et al. IL-10- and TGF-beta-mediated susceptibility in kala-azar and post-kala-azar dermal leishmaniasis: the significance of amphotericin B in the control of Leishmania donovani infection in India. J Immunol. 2007;179(8):5592–5603. doi:10.4049/jimmunol.179.8.5592
  • Santos MF, Alexandre-Pires G, Pereira MA, et al. Immunophenotyping of peripheral blood, lymph node, and bone marrow t lymphocytes during canine leishmaniosis and the impact of antileishmanial chemotherapy. Front Vet Sci. 2020;7. doi:10.3389/fvets.2020.00375
  • Tiwananthagorn S, Iwabuchi K, Ato M, Sakurai T, Kato H, Katakura K. Involvement of CD4+ Foxp3+ regulatory T cells in persistence of leishmania donovani in the liver of alymphoplastic aly/aly mice. PLoS Negl Trop Dis. 2012;6(8):e1798. doi:10.1371/journal.pntd.0001798
  • Roatt BM, Aguiar-Soares RD, Coura-Vital W, et al. Immunotherapy and immunochemotherapy in visceral leishmaniasis: promising treatments for this neglected disease. Front Immunol. 2014;5:272. doi:10.3389/fimmu.2014.00272
  • Ali N, Hussain S. Leishmania donovani bodies in bone marrow. Clin Case Rep. 2014;2(5):238–239. doi:10.1002/ccr3.97
  • Dantas Brito M, Campilho F, Branca R, et al. Visceral leishmaniasis: a differential diagnosis to remember after bone marrow transplantation. Case Rep Hematol. 2014;2014:587912. doi:10.1155/2014/587912
  • Gawade S, Nanaware M, Gokhale R, Adhav P. Visceral leishmaniasis: a case report. Australas Med J. 2012;5(2):130–134. doi:10.4066/AMJ.2012997
  • Dittus C, Semmel D. Leishmania amastigotes visualized on bone marrow aspirate in a leishmaniasis and HIV coinfected patient presenting with pancytopenia. Blood. 2013;122(26):4162. doi:10.1182/blood-2013-08-519306
  • Zhang G, Zhong J, Wang T, Zhong L. Erratum: a case of visceral leishmaniasis found by left oblique hernia: a case report. Exp Ther Med. 2021;21(1):43. doi:10.3892/etm.2020.9477
  • Dirkx L, Hendrickx S, Merlot M, et al. Long-term hematopoietic stem cells as a parasite niche during treatment failure in visceral leishmaniasis. Commun Biol. 2022;5(1):626. doi:10.1038/s42003-022-03591-7
  • Bandeira Ferreira FL, Séguin O, Descoteaux A, Heinonen KM. Persistent cutaneous Leishmania major infection promotes infection-adapted myelopoiesis. Microorganisms. 2022;10(3):535. doi:10.3390/microorganisms10030535
  • Mirkovich AM, Galelli A, Allison AC, Modabber FZ. Increased myelopoiesis during Leishmania major infection in mice: generation of ‘safe targets’, a possible way to evade the effector immune mechanism. Clin Exp Immunol. 1986;64(1):1–7.
  • Richardson C, Yan S, Vestal CG. Oxidative stress, bone marrow failure, and genome instability in hematopoietic stem cells. Int J Mol Sci. 2015;16(2):2366–2385. doi:10.3390/ijms16022366
  • Mangialardi G, Spinetti G, Reni C, Madeddu P. Reactive oxygen species adversely impacts bone marrow microenvironment in diabetes. Antioxid Redox Signal. 2014;21(11):1620–1633. doi:10.1089/ars.2014.5944
  • Porto ML, Rodrigues BP, Menezes TN, et al. Reactive oxygen species contribute to dysfunction of bone marrow hematopoietic stem cells in aged C57BL/6 J mice. J Biomed Sci. 2015;22:97. doi:10.1186/s12929-015-0201-8
  • Zhu H, Kwak HJ, Liu P, et al. Reactive Oxygen species-producing myeloid cells act as a bone marrow niche for sterile inflammation-induced reactive granulopoiesis. J Immunol. 2017;198(7):2854–2864. doi:10.4049/jimmunol.1602006
  • Liu J, Li Y, Chen S, et al. Biomedical application of reactive oxygen species-responsive nanocarriers in cancer, inflammation, and neurodegenerative diseases. Front Chem. 2020;8:838. doi:10.3389/fchem.2020.00838
  • Kulbacka J, Wilk KA, Bazylińska U, Dubińska-Magiera M, Potoczek S, Saczko J. Curcumin loaded nanocarriers with varying charges augmented with electroporation designed for colon cancer therapy. Int J Mol Sci. 2022;23(3):1377. doi:10.3390/ijms23031377
  • Chen Y, Wu X, Li J, Jiang Y, Xu K, Su J. Bone-targeted nanoparticle drug delivery system: an emerging strategy for bone-related disease. Front Pharmacol. 2022;13:909408. doi:10.3389/fphar.2022.909408
  • Mu CF, Shen J, Liang J, et al. Targeted drug delivery for tumor therapy inside the bone marrow. Biomaterials. 2018;155:191–202. doi:10.1016/j.biomaterials.2017.11.029
  • Sou K, Goins B, Oyajobi BO, Travi BL, Phillips WT. Bone marrow-targeted liposomal carriers. Expert Opin Drug Deliv. 2011;8(3):317–328. doi:10.1517/17425247.2011.553218
  • Jiang Y, Lin W, Zhu L. Targeted drug delivery for the treatment of blood cancers. Molecules. 2022;27(4). doi:10.3390/molecules27041310
  • Oliveira LF, Schubach AO, Martins MM, et al. Systematic review of the adverse effects of cutaneous leishmaniasis treatment in the New World. Acta Trop. 2011;118(2):87–96. doi:10.1016/j.actatropica.2011.02.007
  • Stone NR, Bicanic T, Salim R, Hope W. Liposomal Amphotericin B (AmBisome(®)): a review of the pharmacokinetics, pharmacodynamics, clinical experience and future directions. Drugs. 2016;76(4):485–500. doi:10.1007/s40265-016-0538-7
  • Terrazas C, Varikuti S, Oghumu S, et al. Ly6Chi inflammatory monocytes promote susceptibility to Leishmaia donovani infection. Sci Rep. 2017;7(1):14693. doi:10.1038/s41598-017-14935-3
  • Varikuti S, Volpedo G, Saljoughian N, et al. The potent ITK/BTK inhibitor ibrutinib is effective for the treatment of experimental visceral leishmaniasis caused by leishmania donovani. J Infect Dis. 2019;219(4):599–608. doi:10.1093/infdis/jiy552
  • Olingy CE, Dinh HQ, Hedrick CC. Monocyte heterogeneity and functions in cancer. J Leukoc Biol. 2019;106(2):309–322. doi:10.1002/JLB.4RI0818-311R
  • Cortez-Retamozo V, Etzrodt M, Newton A, et al. Angiotensin II drives the production of tumor-promoting macrophages. Immunity. 2013;38(2):296–308. doi:10.1016/j.immuni.2012.10.015
  • (FDA) USFada. VASOTEC®, Enalapril maleate tablets. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/018998_Vasotec.cfm. Accessed June 8, 2023.
  • Ferreira Lopes de Araújo C, Ribeiro da Silva Nunes J, Alexandre Nunes Dos Santos R, Rios Santos F. Leishmaniasis: effect of enalaprilat on the production of (ON) and cytokines in vitro. Res Soc Dev. 2021;10(3). doi:10.33448/rsd-v10i3.12949
  • Miret JJ, Kirschmeier P, Koyama S, et al. Suppression of myeloid cell arginase activity leads to therapeutic response in a NSCLC mouse model by activating anti-tumor immunity. J Immunother Cancer. 2019;7(1):32. doi:10.1186/s40425-019-0504-5
  • Porta C, Consonni FM, Morlacchi S, et al. Tumor-derived prostaglandin E2 promotes p50 NF-κB-dependent differentiation of monocytic MDSCs. Cancer Res. 2020;80(13):2874–2888. doi:10.1158/0008-5472.CAN-19-2843
  • Holtzhausen A, Harris W, Ubil E, et al. TAM family receptor kinase inhibition reverses MDSC-mediated suppression and augments anti-PD-1 therapy in melanoma. Cancer Immunol Res. 2019;7(10):1672–1686. doi:10.1158/2326-6066.CIR-19-0008
  • Nefedova Y, Nagaraj S, Rosenbauer A, Muro-Cacho C, Sebti SM, Gabrilovich DI. Regulation of dendritic cell differentiation and antitumor immune response in cancer by pharmacologic-selective inhibition of the janus-activated kinase 2/signal transducers and activators of transcription 3 pathway. Cancer Res. 2005;65(20):9525–9535. doi:10.1158/0008-5472.CAN-05-0529
  • de Souza A, Marins DSS, Mathias SL, et al. Promising nanotherapy in treating leishmaniasis. Int J Pharm. 2018;547(1–2):421–431. doi:10.1016/j.ijpharm.2018.06.018
  • Dalle Vedove E, Costabile G, Merkel OM. Mannose and mannose-6-phosphate receptor-targeted drug delivery systems and their application in cancer therapy. Adv Healthc Mater. 2018;7(14):e1701398. doi:10.1002/adhm.201701398
  • Pan Z, Kang X, Zeng Y, et al. A mannosylated PEI–CPP hybrid for TRAIL gene targeting delivery for colorectal cancer therapy. Polym Chem. 2017;8(35):5275–5285. doi:10.1039/C7PY00882A
  • Dar MJ, Din FU, Khan GM. Sodium stibogluconate loaded nano-deformable liposomes for topical treatment of leishmaniasis: macrophage as a target cell. Drug Deliv. 2018;25(1):1595–1606. doi:10.1080/10717544.2018.1494222
  • Gélvez APC, Diniz Junior JAP, Brígida RTSS, Rodrigues APD. AgNP-PVP-meglumine antimoniate nanocomposite reduces Leishmania amazonensis infection in macrophages. BMC Microbiol. 2021;21(1):211. doi:10.1186/s12866-021-02267-2
  • Matsushita M, Freigang S, Schneider C, Conrad M, Bornkamm GW, Kopf M. T cell lipid peroxidation induces ferroptosis and prevents immunity to infection. J Exp Med. 2015;212(4):555–568. doi:10.1084/jem.20140857
  • Lőrincz T, Holczer M, Kapuy O, Szarka A. The interrelationship of pharmacologic ascorbate induced cell death and ferroptosis. Pathol Oncol Res. 2019;25(2):669–679. doi:10.1007/s12253-018-0539-9
  • Urrutia P, Aguirre P, Esparza A, et al. Inflammation alters the expression of DMT1, FPN1 and hepcidin, and it causes iron accumulation in central nervous system cells. J Neurochem. 2013;126(4):541–549. doi:10.1111/jnc.12244
  • Jarvis JN, Meintjes G, Bicanic T, et al. Cerebrospinal fluid cytokine profiles predict risk of early mortality and immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis. PLoS Pathog. 2015;11(4):e1004754. doi:10.1371/journal.ppat.1004754
  • Xiao L, Huang H, Fan S, et al. Ferroptosis: a mixed blessing for infectious diseases. Front Pharmacol. 2022;13:992734. doi:10.3389/fphar.2022.992734
  • Spangler B, Morgan CW, Fontaine SD, et al. A reactivity-based probe of the intracellular labile ferrous iron pool. Nat Chem Biol. 2016;12(9):680–685. doi:10.1038/nchembio.2116
  • Sato K, Shi L, Ito F, et al. Non-thermal plasma specifically kills oral squamous cell carcinoma cells in a catalytic Fe(II)-dependent manner. J Clin Biochem Nutr. 2019;65(1):8–15. doi:10.3164/jcbn.18-91
  • Brown CW, Amante JJ, Chhoy P, et al. Prominin2 drives ferroptosis resistance by stimulating iron export. Dev Cell. 2019;51(5):575–586.e4. doi:10.1016/j.devcel.2019.10.007
  • Alvarez SW, Sviderskiy VO, Terzi EM, et al. Author Correction: NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis. Nature. 2022;609(7929):E12. doi:10.1038/s41586-022-05323-7
  • Wang W, Green M, Choi JE, et al. CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy. Nature. 2019;569(7755):270–274. doi:10.1038/s41586-019-1170-y
  • Gaschler MM, Andia AA, Liu H, et al. FINO2 initiates ferroptosis though GPX4 inactivation and iron oxidation. Nat Chem Biol. 2018;14(5):507–515. doi:10.1038/s41589-018-0031-6
  • Ryu MS, Zhang D, Protchenko O, Shakoury-Elizeh M, Philpott CC. PCBP1 and NCOA4 regulate erythroid iron storage and heme biosynthesis. J Clin Invest. 2017;127(5):1786–1797. doi:10.1172/JCI90519
  • McGrath KE, Frame JM, Palis J. Early hematopoiesis and macrophage development. Semin Immunol. 2015;27(6):379–387. doi:10.1016/j.smim.2016.03.013
  • Liu D, Uzonna JE. The early interaction of Leishmania with macrophages and dendritic cells and its influence on the host immune response. Front Cell Infect Microbiol. 2012;2:83. doi:10.3389/fcimb.2012.00083
  • Lee SH, Charmoy M, Romano A, et al. Mannose receptor high, M2 dermal macrophages mediate nonhealing Leishmania major infection in a Th1 immune environment. J Exp Med. 2018;215(1):357–375. doi:10.1084/jem.20171389
  • Woelbing F, Kostka SL, Moelle K, et al. Uptake of Leishmania major by dendritic cells is mediated by Fcgamma receptors and facilitates acquisition of protective immunity. J Exp Med. 2006;203(1):177–188. doi:10.1084/jem.20052288
  • Raybarman C, Bhattacharjee S. Central and local controls of monocytopoiesis influence the outcome of Leishmania infection. Cytokine. 2021;147:155325. doi:10.1016/j.cyto.2020.155325
  • Matte C, Arango Duque G, Descoteaux A. Leishmania donovani metacyclic promastigotes impair phagosome properties in inflammatory monocytes. Infect Immun. 2021;89(7):e0000921. doi:10.1128/IAI.00009-21
  • Romano A, Carneiro MBH, Doria NA, et al. Divergent roles for Ly6C+CCR2+CX3CR1+ inflammatory monocytes during primary or secondary infection of the skin with the intra-phagosomal pathogen Leishmania major. PLoS Pathog. 2017;13(6):e1006479. doi:10.1371/journal.ppat.1006479
  • Goncalves R, Zhang X, Cohen H, Debrabant A, Mosser DM. Platelet activation attracts a subpopulation of effector monocytes to sites of Leishmania major infection. J Exp Med. 2011;208(6):1253–1265. doi:10.1084/jem.20101751
  • Sato N, Ahuja SK, Quinones M, et al. CC chemokine receptor (CCR)2 is required for Langerhans cell migration and localization of T helper cell type 1 (Th1)-inducing dendritic cells. Absence of CCR2 shifts the Leishmania major-resistant phenotype to a susceptible state dominated by Th2 cytokines, b cell outgrowth, and sustained neutrophilic inflammation. J Exp Med. 2000;192(2):205–218. doi:10.1084/jem.192.2.205
  • Quinones MP, Estrada CA, Jimenez F, et al. CCL2-independent role of CCR2 in immune responses against Leishmania major. Parasite Immunol. 2007;29(4):211–217. doi:10.1111/j.1365-3024.2006.00935.x
  • de Freitas EO, Leoratti FM, Freire-de-lima CG, Morrot A, Feijó DF. The contribution of immune evasive mechanisms to parasite persistence in visceral leishmaniasis. Front Immunol. 2016;7:153. doi:10.3389/fimmu.2016.00153
  • Lambertz U, Silverman JM, Nandan D, et al. Secreted virulence factors and immune evasion in visceral leishmaniasis. J Leukoc Biol. 2012;91(6):887–899. doi:10.1189/jlb.0611326
  • Cecílio P, Pérez-Cabezas B, Santarém N, Maciel J, Rodrigues V, Cordeiro da Silva A. Deception and manipulation: the arms of leishmania, a successful parasite. Front Immunol. 2014;5:480. doi:10.3389/fimmu.2014.00480
  • Murray HW, Nathan CF. Macrophage microbicidal mechanisms in vivo: reactive nitrogen versus oxygen intermediates in the killing of intracellular visceral Leishmania donovani. J Exp Med. 1999;189(4):741–746. doi:10.1084/jem.189.4.741
  • Boitz JM, Gilroy CA, Olenyik TD, et al. Arginase is essential for survival of leishmania donovani promastigotes but not intracellular amastigotes. Infect Immun. 2017;85(1). doi:10.1128/IAI.00554-16
  • Singh N, Kumar R, Chauhan SB, Engwerda C, Sundar S. Peripheral blood monocytes with an antiinflammatory phenotype display limited phagocytosis and oxidative burst in patients with visceral leishmaniasis. J Infect Dis. 2018;218(7):1130–1141. doi:10.1093/infdis/jiy228
  • Viana AG, Magalhães LMD, Giunchetti RC, Dutra WO, Gollob KJ. Infection of human monocytes with Leishmania infantum strains induces a downmodulated response when compared with infection with Leishmania brazilensis. Front Immunol. 2017;8:1896. doi:10.3389/fimmu.2017.01896
  • Pereira WF, Ribeiro-Gomes FL, Guillermo LV, et al. Myeloid-derived suppressor cells help protective immunity to Leishmania major infection despite suppressed T cell responses. J Leukoc Biol. 2011;90(6):1191–1197. doi:10.1189/jlb.1110608
  • Formaglio P, Alabdullah M, Siokis A, et al. Nitric oxide controls proliferation of Leishmania major by inhibiting the recruitment of permissive host cells. Immunity. 2021;54(12):2724–2739.e10. doi:10.1016/j.immuni.2021.09.021
  • Postat J, Olekhnovitch R, Lemaître F, Bousso P. A metabolism-based quorum sensing mechanism contributes to termination of inflammatory responses. Immunity. 2018;49(4):654–665.e5. doi:10.1016/j.immuni.2018.07.014
  • Husain MJ, Datta BK, Kostova D, et al. Access to cardiovascular disease and hypertension medicines in developing countries: an analysis of essential medicine lists, price, availability, and affordability. J Am Heart Assoc. 2020;9(9):e015302. doi:10.1161/JAHA.119.015302
  • Vellozo NS, Rigoni TS, Lopes MF. New Therapeutic Tools to Shape Monocyte Functional Phenotypes in Leishmaniasis. Front Immunol. 2021;12:704429. doi:10.3389/fimmu.2021.704429
  • Roy S, Mukhopadhyay D, Mukherjee S, et al. An IL-10 dominant polarization of monocytes is a feature of Indian Visceral Leishmaniasis. Parasite Immunol. 2018;40(7):e12535. doi:10.1111/pim.12535
  • Pacheco-Fernandez T, Volpedo G, Verma C, Satoskar AR. Understanding the immune responses involved in mediating protection or immunopathology during leishmaniasis. Biochem Soc Trans. 2021;49(1):297–311. doi:10.1042/BST20200606
  • Hume DA, Irvine KM, Pridans C. The Mononuclear Phagocyte System: the Relationship between Monocytes and Macrophages. Trends Immunol. 2019;40(2):98–112. doi:10.1016/j.it.2018.11.007
  • Oliveira WN, Ribeiro LE, Schrieffer A, Machado P, Carvalho EM, Bacellar O. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of human tegumentary leishmaniasis. Cytokine. 2014;66(2):127–132. doi:10.1016/j.cyto.2013.12.016
  • Bogdan C. Macrophages as host, effector and immunoregulatory cells in leishmaniasis: impact of tissue micro-environment and metabolism. Cytokine X. 2020;2(4):100041. doi:10.1016/j.cytox.2020.100041
  • Scott P, Novais FO. Cutaneous leishmaniasis: immune responses in protection and pathogenesis. Nat Rev Immunol. 2016;16(9):581–592. doi:10.1038/nri.2016.72
  • Vellozo NS, Ribiero-Gomes FL, Lopes MF. Shifting macrophage phenotypes in leishmaniasis. In: Kumar V, editor. Macrophages Celebrating 140 Years of Discovery. Intech Open; 2022:392.
  • Du H, Levine M, Ganesa C, Witte DP, Cole ES, Grabowski GA. The role of mannosylated enzyme and the mannose receptor in enzyme replacement therapy. Am J Hum Genet. 2005;77(6):1061–1074. doi:10.1086/498652
  • Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149(5):1060–1072. doi:10.1016/j.cell.2012.03.042
  • Bersuker K, Hendricks JM, Li Z, et al. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature. 2019;575(7784):688–692. doi:10.1038/s41586-019-1705-2
  • Cheng Z, Li Y. What is responsible for the initiating chemistry of iron-mediated lipid peroxidation: an update. Chem Rev. 2007;107(3):748–766. doi:10.1021/cr040077w
  • Halliwell B, Chirico S. Lipid peroxidation: its mechanism, measurement, and significance. Am J Clin Nutr. 1993;57(5 Suppl):715S–724S. doi:10.1093/ajcn/57.5.715S
  • Brigelius-Flohé R, Maiorino M. Glutathione peroxidases. Biochim Biophys Acta. 2013;1830(5):3289–3303. doi:10.1016/j.bbagen.2012.11.020
  • Yang WS, SriRamaratnam R, Welsch ME, et al. Regulation of ferroptotic cancer cell death by GPX4. Cell. 2014;156(1–2):317–331. doi:10.1016/j.cell.2013.12.010
  • Gao M, Monian P, Quadri N, Ramasamy R, Jiang X. Glutaminolysis and transferrin regulate ferroptosis. Mol Cell. 2015;59(2):298–308. doi:10.1016/j.molcel.2015.06.011
  • Zhang Y, Swanda RV, Nie L, et al. mTORC1 couples cyst(e)ine availability with GPX4 protein synthesis and ferroptosis regulation. Nat Commun. 2021;12(1):1589. doi:10.1038/s41467-021-21841-w
  • Moreira DS, Xavier MV, Murta SMF. Ascorbate peroxidase overexpression protects Leishmania braziliensis against trivalent antimony effects. Mem Inst Oswaldo Cruz. 2018;113(12):e180377. doi:10.1590/0074-02760180377
  • Zhang Z, Zhang L, Zhou L, Lei Y, Zhang Y, Huang C. Redox signaling and unfolded protein response coordinate cell fate decisions under ER stress. Redox Biol. 2019;25:101047. doi:10.1016/j.redox.2018.11.005
  • Andrade JM, Murta SM. Functional analysis of cytosolic tryparedoxin peroxidase in antimony-resistant and -susceptible Leishmania braziliensis and Leishmania infantum lines. Parasit Vectors. 2014;7:406. doi:10.1186/1756-3305-7-406
  • Kumar A, Das S, Purkait B, et al. Ascorbate peroxidase, a key molecule regulating amphotericin B resistance in clinical isolates of Leishmania donovani. Antimicrob Agents Chemother. 2014;58(10):6172–6184. doi:10.1128/AAC.02834-14
  • Das S, Giri S, Sundar S, Shaha C. Functional involvement of leishmania donovani tryparedoxin peroxidases during infection and drug treatment. Antimicrob Agents Chemother. 2018;62(1). doi:10.1128/AAC.00806-17
  • Pal S, Dolai S, Yadav RK, Adak S. Ascorbate peroxidase from Leishmania major controls the virulence of infective stage of promastigotes by regulating oxidative stress. PLoS One. 2010;5(6):e11271. doi:10.1371/journal.pone.0011271
  • Mukherjee A, Boisvert S, Monte-Neto RL, et al. Telomeric gene deletion and intrachromosomal amplification in antimony-resistant Leishmania. Mol Microbiol. 2013;88(1):189–202. doi:10.1111/mmi.12178
  • Soares MP, Hamza I. Macrophages and iron metabolism. Immunity. 2016;44(3):492–504. doi:10.1016/j.immuni.2016.02.016
  • Laranjeira-Silva MF, Hamza I, Pérez-Victoria JM. Iron and heme metabolism at the leishmania-host interface. Trends Parasitol. 2020;36(3):279–289. doi:10.1016/j.pt.2019.12.010
  • Kristiansen M, Graversen JH, Jacobsen C, et al. Identification of the haemoglobin scavenger receptor. Nature. 2001;409(6817):198–201. doi:10.1038/35051594
  • Morimoto A, Omachi S, Osada Y, et al. Hemophagocytosis in experimental visceral leishmaniasis by leishmania donovani. PLoS Negl Trop Dis. 2016;10(3):e0004505. doi:10.1371/journal.pntd.0004505
  • Pham NK, Mouriz J, Kima PE. Leishmania pifanoi amastigotes avoid macrophage production of superoxide by inducing heme degradation. Infect Immun. 2005;73(12):8322–8333. doi:10.1128/IAI.73.12.8322-8333.2005
  • Silva RL, Santos MB, Almeida PL, et al. sCD163 levels as a biomarker of disease severity in leprosy and visceral leishmaniasis. PLoS Negl Trop Dis. 2017;11(3):e0005486. doi:10.1371/journal.pntd.0005486
  • Docampo R, de Boiso JF, Boveris A, Stoppani AO. Localization of peroxidase activity in Trypanosoma cruzi microbodies. Experientia. 1976;32(8):972–975. doi:10.1007/BF01933918
  • Boveris A, Sies H, Martino EE, Docampo R, Turrens JF, Stoppani AO. Deficient metabolic utilization of hydrogen peroxide in Trypanosoma cruzi. Biochem J. 1980;188(3):643–648. doi:10.1042/bj1880643
  • Clark D, Albrecht M, Arévalo J. Ascorbate variations and dehydroascorbate reductase activity in Trypanosoma cruzi epimastigotes and trypomastigotes. Mol Biochem Parasitol. 1994;66(1):143–145. doi:10.1016/0166-6851(94)90045-0
  • Bogacz M, Krauth-Siegel RL. Tryparedoxin peroxidase-deficiency commits trypanosomes to ferroptosis-type cell death. Elife. 2018;7. doi:10.7554/eLife.37503
  • Cotter C, Sturrock HJ, Hsiang MS, et al. The changing epidemiology of malaria elimination: new strategies for new challenges. Lancet. 2013;382(9895):900–911. doi:10.1016/S0140-6736(13)60310-4
  • Singh KS, Leu JI, Barnoud T, et al. Author Correction: African-centric TP53 variant increases iron accumulation and bacterial pathogenesis but improves response to malaria toxin. Nat Commun. 2020;11(1):1541. doi:10.1038/s41467-020-15366-x
  • Yao Y, Chen Z, Zhang H, et al. Selenium-GPX4 axis protects follicular helper T cells from ferroptosis. Nat Immunol. 2021;22(9):1127–1139. doi:10.1038/s41590-021-00996-0
  • Imlay JA, Chin SM, Linn S. Toxic DNA damage by hydrogen peroxide through the Fenton reaction in vivo and in vitro. Science. 1988;240(4852):640–642. doi:10.1126/science.2834821
  • Rodriguez GM. Control of iron metabolism in Mycobacterium tuberculosis. Trends Microbiol. 2006;14(7):320–327. doi:10.1016/j.tim.2006.05.006
  • Amaral EP, Costa DL, Namasivayam S, et al. A major role for ferroptosis in Mycobacterium tuberculosis-induced cell dead in tissue necrosis. J Exp Med. 2019;216(3):556–570. doi:10.1084/jem.20181776
  • Xu X, Lin D, Tu S, Gao S, Shao A, Sheng J. Is ferroptosis a future direction in exploring cryptococcal meningitis? Front Immunol. 2021;12:598601. doi:10.3389/fimmu.2021.598601
  • Barluzzi R, Saleppico S, Nocentini A, et al. Iron overload exacerbates experimental meningoencephalitis by Cryptococcus neoformans. J Neuroimmunol. 2002;132(1–2):140–146. doi:10.1016/s0165-5728(02)00324-7
  • Hassannia B, Wiernicki B, Ingold I, et al. Nano-targeted induction of dual ferroptotic mechanisms eradicates high-risk neuroblastoma. J Clin Invest. 2018;128(8):3341–3355. doi:10.1172/JCI99032
  • Rothe T, Gruber F, Uderhardt S, et al. 12/15-Lipoxygenase-mediated enzymatic lipid oxidation regulates DC maturation and function. J Clin Invest. 2015;125(5):1944–1954. doi:10.1172/JCI78490
  • Cramer SL, Saha A, Liu J, et al. Systemic depletion of L-cyst(e)ine with cyst(e)inase increases reactive oxygen species and suppresses tumor growth. Nat Med. 2017;23(1):120–127. doi:10.1038/nm.4232
  • Yan HF, Zou T, Tuo QZ, et al. Ferroptosis: mechanisms and links with diseases. Signal Transduct Target Ther. 2021;6(1):49. doi:10.1038/s41392-020-00428-9