4,437
Views
2
CrossRef citations to date
0
Altmetric
Review

Autophagy, cell death, and cytokines in K. pneumoniae infection: therapeutic perspectives

, , &
Article: 2140607 | Received 03 Jul 2022, Accepted 21 Oct 2022, Published online: 18 Dec 2022

References

  • De Oliveira DMP, Forde BM, Kidd TJ, et al. Antimicrobial resistance in ESKAPE pathogens. Clin Microbiol Rev. 2020 Jun 17;33(3):e00181-19.
  • Zhou K, Xiao T, David S, et al. Novel subclone of carbapenem-resistant Klebsiella pneumoniae sequence type 11 with enhanced virulence and transmissibility, China. Emerg Infect Dis. 2020 Feb;26(2):289–297.
  • Gu D, Dong N, Zheng Z, et al. A fatal outbreak of ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae in a Chinese hospital: a molecular epidemiological study. Lancet Infect Dis. 2018;18(1):37–46.
  • Bengoechea JA, Sa Pessoa J. Klebsiella pneumoniae infection biology: living to counteract host defences. FEMS Microbiol Rev. 2019 Mar 1;43(2):123–144.
  • Diago-Navarro E, Calatayud-Baselga I, Sun D, et al. Antibody-based immunotherapy to treat and prevent infection with hypervirulent Klebsiella pneumoniae. Clin Vaccine Immunol. 2017;24(1):e00456-16.
  • Donta ST, Peduzzi P, Cross AS, et al. Immunoprophylaxis against Klebsiella and pseudomonas Aeruginosa infections. The federal hyperimmune immunoglobulin trial study group. J Infect Dis. 1996;174(3):537–543.
  • Liu M, Li W, Xiang X, et al. Mycobacterium tuberculosis effectors interfering host apoptosis signaling. Apoptosis. 2015;20(7):883–891.
  • Etna MP, Giacomini E, Severa M, et al. Pro- and anti-inflammatory cytokines in tuberculosis: a two-edged sword in TB pathogenesis. Semin Immunol. 2014;26(6):543–551.
  • Periselneris J, Ercoli G, Pollard T, et al. Relative contributions of extracellular and internalized bacteria to early macrophage proinflammatory responses to Streptococcus pneumoniae. mBio. 2019;10(5):e02144-19.
  • Zhang Y, Yao Y, Qiu X, et al. Listeria hijacks host mitophagy through a novel mitophagy receptor to evade killing. Nat Immunol. 2019;20(4):433–446.
  • Wanford JJ, Hames RG, Carreno D, et al. Interaction of Klebsiella pneumoniae with tissue macrophages in a mouse infection model and ex-vivo pig organ perfusions: an exploratory investigation. The Lancet Microbe. 2021;2(12):e695–e703.
  • Cano V, March C, Insua JL, et al. Klebsiella pneumoniae survives within macrophages by avoiding delivery to lysosomes. Cell Microbiol. 2015;17(11):1537–1560.
  • Paczosa MK, Mecsas J. Klebsiella pneumoniae: going on the offense with a strong defense. Microbiol Mol Biol Rev: MMBR. 2016;80(3):629–661.
  • Martin RM, Bachman MA. Colonization, infection, and the accessory genome of Klebsiella pneumoniae. Front Cell Infect Microbiol. 2018;8(4).
  • Donskey CJ. The role of the intestinal tract as a reservoir and source for transmission of nosocomial pathogens. Clin Infect Dis. 2004;39(2):219–226.
  • Martin RM, Cao J, Brisse S, et al. Molecular epidemiology of colonizing and infecting isolates of Klebsiella pneumoniae. mSphere. 2016;1(5):e00261-16.
  • Human Microbiome Project C. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486(7402):207–214.
  • Li B, Zhao Y, Liu C, et al. Molecular pathogenesis of Klebsiella pneumoniae. Future Microbiol. 2014;9(9):1071–1081.
  • Struve C, Bojer M, Krogfelt KA. Characterization of Klebsiella pneumoniae type 1 fimbriae by detection of phase variation during colonization and infection and impact on virulence. Infect Immun. 2008;76(9):4055–4065.
  • Struve C, Bojer M, Krogfelt KA. Identification of a conserved chromosomal region encoding Klebsiella pneumoniae type 1 and type 3 fimbriae and assessment of the role of fimbriae in pathogenicity. Infect Immun. 2009;77(11):5016–5024.
  • Sahly H, Keisari Y, Crouch E, et al. Recognition of bacterial surface polysaccharides by lectins of the innate immune system and its contribution to defense against infection: the case of pulmonary pathogens. Infect Immun. 2008;76(4):1322–1332.
  • Stahlhut SG, Struve C, Krogfelt KA. Klebsiella pneumoniae type 3 fimbriae agglutinate yeast in a mannose-resistant manner. J Med Microbiol. 2012;61(Pt 3):317–322.
  • Przondo-Mordarska A, Ko HL, Beuth J, et al. Chemiluminescence response of human polymorphonuclear leukocytes induced by purified, latex attached Klebsiella fimbriae. Z Bakteriologie: Int J Med Microbiol. 1991;275(4):521–529.
  • Lavender H, Jagnow JJ, Clegg S. Klebsiella pneumoniae type 3 fimbria-mediated immunity to infection in the murine model of respiratory disease. Int J Med Microbiol: IJMM. 2005;295(3):153–159.
  • Sequeira RP, McDonald JAK, Marchesi JR, et al. Commensal Bacteroidetes protect against Klebsiella pneumoniae colonization and transmission through IL-36 signalling. Nat Microbiol. 2020;5(2):304–313.
  • Clements A, Tull D, Jenney AW, et al. Secondary acylation of Klebsiella pneumoniae lipopolysaccharide contributes to sensitivity to antibacterial peptides. J Biol Chem. 2007;282(21):15569–15577.
  • Doorduijn DJ, Rooijakkers SH, van Schaik W, et al. Complement resistance mechanisms of Klebsiella pneumoniae. Immunobiology. 2016;221(10):1102–1109.
  • Tan YH, Chen Y, Chu WHW, et al. Cell envelope defects of different capsule-null mutants in K1 hypervirulent Klebsiella pneumoniae can affect bacterial pathogenesis. Mol Microbiol. 2020;113(5):889–905.
  • Campos MA, Vargas MA, Regueiro V, et al. Capsule polysaccharide mediates bacterial resistance to antimicrobial peptides. Infect Immun. 2004;72(12):7107–7114.
  • Moranta D, Regueiro V, March C, et al. Klebsiella pneumoniae capsule polysaccharide impedes the expression of beta-defensins by airway epithelial cells. Infect Immun. 2010;78(3):1135–1146.
  • Yoshida K, Matsumoto T, Tateda K, et al. Role of bacterial capsule in local and systemic inflammatory responses of mice during pulmonary infection with Klebsiella pneumoniae. J Med Microbiol. 2000;49(11):1003–1010.
  • Evrard B, Balestrino D, Dosgilbert A, et al. Roles of capsule and lipopolysaccharide O antigen in interactions of human monocyte-derived dendritic cells and Klebsiella pneumoniae. Infect Immun. 2010;78(1):210–219.
  • Yoshida K, Matsumoto T, Tateda K, et al. Induction of interleukin-10 and down-regulation of cytokine production by Klebsiella pneumoniae capsule in mice with pulmonary infection. J Med Microbiol. 2001;50(5):456–461.
  • Regueiro V, Moranta D, Frank CG, et al. Klebsiella pneumoniae subverts the activation of inflammatory responses in a NOD1-dependent manner. Cell Microbiol. 2011;13(1):135–153.
  • Walker KA, Treat LP, Sepulveda VE, et al. The small protein RmpD drives hypermucoviscosity in Klebsiella pneumoniae. mBio. 2020;11(5):e01750-20.
  • Sa-Pessoa J, Przybyszewska K, Vasconcelos FN, et al. Klebsiella pneumoniae reduces SUMOylation to limit host defense responses. mBio. 2020;11(5):e01733-20.
  • Kobayashi SD, Porter AR, Freedman B, et al. Antibody-mediated killing of carbapenem-resistant ST258 Klebsiella pneumoniae by human neutrophils. mBio. 2018;9(2):e00297-18.
  • Lee CH, Chang CC, Liu JW, et al. Sialic acid involved in hypermucoviscosity phenotype of Klebsiella pneumoniae and associated with resistance to neutrophil phagocytosis. Virulence. 2014;5(6):673–679.
  • Follador R, Heinz E, Wyres KL, et al. The diversity of Klebsiella pneumoniae surface polysaccharides. Microbial Genomics. 2016;2(8):e000073.
  • Sahly H, Aucken H, Benedi VJ, et al. Impairment of respiratory burst in polymorphonuclear leukocytes by extended-spectrum beta-lactamase-producing strains of Klebsiella pneumoniae. Eur J Clin Microbiol Infect Dis. 2004;23(1):20–26.
  • Merle NS, Noe R, Halbwachs-Mecarelli L, et al. Complement system part II: role in immunity. Front Immunol. 2015;6:257.
  • Shankar-Sinha S, Valencia GA, Janes BK, et al. The Klebsiella pneumoniae O antigen contributes to bacteremia and lethality during murine pneumonia. Infect Immun. 2004;72(3):1423–1430.
  • Cortes G, Borrell N, de Astorza B, et al. Molecular analysis of the contribution of the capsular polysaccharide and the lipopolysaccharide O side chain to the virulence of Klebsiella pneumoniae in a murine model of pneumonia. Infect Immun. 2002;70(5):2583–2590.
  • Willingham SB, Allen IC, Bergstralh DT, et al. NLRP3 (NALP3, Cryopyrin) facilitates in vivo caspase-1 activation, necrosis, and HMGB1 release via inflammasome-dependent and -independent pathways. J Immunol. 2009;183(3):2008–2015.
  • Greco E, Quintiliani G, Santucci MB, et al. Janus-faced liposomes enhance antimicrobial innate immune response in Mycobacterium tuberculosis infection. Proc Natl Acad Sci U S A. 2012 May 22;109(21):E1360–8.
  • Fevre C, Almeida AS, Taront S, et al. A novel murine model of rhinoscleroma identifies Mikulicz cells, the disease signature, as IL-10 dependent derivatives of inflammatory monocytes. EMBO Mol Med. 2013;5(4):516–530.
  • Miethke M, Marahiel MA. Siderophore-based iron acquisition and pathogen control. Microbiol Mol Biol Rev: MMBR. 2007;71(3):413–451.
  • Shon AS, Bajwa RP, Russo TA. Hypervirulent (hypermucoviscous) Klebsiella pneumoniae: a new and dangerous breed. Virulence. 2013;4(2):107–118.
  • Bachman MA, Lenio S, Schmidt L, et al. Interaction of lipocalin 2, transferrin, and siderophores determines the replicative niche of Klebsiella pneumoniae during pneumonia. mBio. 2012;3(6):e00224-11.
  • March C, Moranta D, Regueiro V, et al. Klebsiella pneumoniae outer membrane protein A is required to prevent the activation of airway epithelial cells. J Biol Chem. 2011;286(12):9956–9967.
  • Jeannin P, Renno T, Goetsch L, et al. Ompa targets dendritic cells, induces their maturation and delivers antigen into the MHC class I presentation pathway. Nat Immunol. 2000;1(6):502–509.
  • Soulas C, Baussant T, Aubry JP, et al. Outer membrane protein A (OmpA) binds to and activates human macrophages. J Immunol. 2000;165(5):2335–2340.
  • Pichavant M, Delneste Y, Jeannin P, et al. Outer membrane protein A from Klebsiella pneumoniae activates bronchial epithelial cells: implication in neutrophil recruitment. J Immunol. 2003;171(12):6697–6705.
  • Llobet E, March C, Gimenez P, et al. Klebsiella pneumoniae OmpA confers resistance to antimicrobial peptides. Antimicrob Agents Chemother. 2009;53(1):298–302.
  • You HS, Lee SH, Kang SS, et al. Ompa of Klebsiella pneumoniae ATCC 13883 induces pyroptosis in HEp-2 cells, leading to cell-cycle arrest and apoptosis. Microbes Infect. 2020;22(9):432–440.
  • Tsai YK, Fung CP, Lin JC, et al. Klebsiella pneumoniae outer membrane porins OmpK35 and OmpK36 play roles in both antimicrobial resistance and virulence. Antimicrob Agents Chemother. 2011;55(4):1485–1493.
  • March C, Cano V, Moranta D, et al. Role of bacterial surface structures on the interaction of Klebsiella pneumoniae with phagocytes. PloS one. 2013;8(2):e56847.
  • Bialek-Davenet S, Lavigne JP, Guyot K, et al. Differential contribution of AcrAB and OqxAB efflux pumps to multidrug resistance and virulence in Klebsiella pneumoniae. J Antimicrob Chemother. 2015;70(1):81–88.
  • Wang X, Chen H, Zhang Y, et al. Genetic characterisation of clinical Klebsiella pneumoniae isolates with reduced susceptibility to tigecycline: role of the global regulator RamA and its local repressor RamR. Int J Antimicrob Agents. 2015;45(6):635–640.
  • Padilla E, Llobet E, Domenech-Sanchez A, et al. Klebsiella pneumoniae AcrAB efflux pump contributes to antimicrobial resistance and virulence. Antimicrob Agents Chemother. 2010;54(1):177–183.
  • Stamm CE, Pasko BL, Chaisavaneeyakorn S, et al. Screening Mycobacterium tuberculosis secreted proteins identifies Mpt64 as a eukaryotic membrane-binding bacterial effector. mSphere. 2019;4(3):e00354-19.
  • Shirani I, Zhang H, Zhao G, et al. In silico identification of novel immunogenic secreted proteins of Mycoplasma bovis from secretome data and experimental verification. Pathogens. 2020;9(9):770.
  • Satchidanandam V, Kumar N, Biswas S, et al. The secreted protein Rv1860 of Mycobacterium tuberculosis stimulates human polyfunctional CD8+ T cells. Clin Vacc Immunol. 2016;23(4):282–293.
  • Trajkovic V. [The role of mycobacterial secretory proteins in immune response in tuberculosis]. Med Pregl. 2004;57(Suppl 1):25–28.
  • Brinkworth AJ, Hammer CH, Olano LR, et al. Identification of outer membrane and exoproteins of carbapenem-resistant multilocus sequence type 258 Klebsiella pneumoniae. PloS one. 2015;10(4):e0123219.
  • Lin TL, Chuang YP, Huang YT, et al. Identification of an immuno-dominant protein from Klebsiella pneumoniae strains causing pyogenic liver abscess: implication in serodiagnosis. BMC Microbiol. 2014;14:321.
  • Levine B, Deretic V. unveiling the roles of autophagy in innate and adaptive immunity. Nat Rev Immunol. 2007;7(10):767–777.
  • Ktistakis NT, Tooze SA. Digesting the expanding mechanisms of autophagy. Trends Cell Biol. 2016;26(8):624–635.
  • Hu W, Chan H, Lu L, et al. Autophagy in intracellular bacterial infection. Semin Cell Dev Biol. 2020;101:41–50.
  • Shi Z, Li G, Zhang L, et al. Klebsiella pneumoniae infection inhibits autophagy by alveolar type II epithelial cells. Exp Ther Med. 2020 Oct;20(4):3703–3708.
  • Rekha RS, Karadottir H, Ahmed S, et al. Innate effector systems in primary human macrophages sensitize multidrug-resistant Klebsiella pneumoniae to antibiotics. Infect Immun. 2020;88(8):e00186-20.
  • Nikouee A, Kim M, Ding X, et al. Beclin-1-dependent autophagy improves outcomes of pneumonia-induced sepsis. Front Cell Infect Microbiol. 2021;11:706637.
  • Wang Y, Zhang H. Regulation of autophagy by mTOR signaling pathway. Adv Exp Med Biol. 2019;1206:67–83.
  • Heras-Sandoval D, Perez-Rojas JM, Hernandez-Damian J, et al. The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration. Cell Signal. 2014;26(12):2694–2701.
  • Kamaladevi A, Balamurugan K. Global proteomics revealed Klebsiella pneumoniae induced autophagy and oxidative stress in Caenorhabditis elegans by inhibiting PI3K/AKT/mTOR pathway during infection. Front Cell Infect Microbiol. 2017;7:393.
  • Bah A, Vergne I. Macrophage autophagy and bacterial infections. Front Immunol. 2017;8:1483.
  • Watson RO, Manzanillo PS, Cox JS. Extracellular M. tuberculosis DNA targets bacteria for autophagy by activating the host DNA-sensing pathway. Cell. 2012;150(4):803–815.
  • Ye Y, Tan S, Zhou X, et al. Inhibition of p-IkappaBalpha ubiquitylation by autophagy-related gene 7 to regulate inflammatory responses to bacterial infection. J Infect Dis. 2015;212(11):1816–1826.
  • Sharma A, Simonson TJ, Jondle CN, et al. Mincle-Mediated neutrophil extracellular trap formation by regulation of autophagy. J Infect Dis. 2017;215(7):1040–1048.
  • Tripathi JK, Sharma A, Sukumaran P, et al. Oxidant sensor cation channel TRPM2 regulates neutrophil extracellular trap formation and protects against pneumoseptic bacterial infection. FASEB J. 2018;32(12):6848–6859.
  • Wang K, Chen Y, Zhang P, et al. Protective features of autophagy in pulmonary infection and inflammatory diseases. Cells. 2019 Feb 3;8(2):123.
  • Sharma A, Steichen AL, Jondle CN, et al. Protective role of Mincle in bacterial pneumonia by regulation of neutrophil mediated phagocytosis and extracellular trap formation. J Infect Dis. 2014;209(11):1837–1846.
  • Li X, He S, Zhou X, et al. Lyn delivers bacteria to lysosomes for eradication through TLR2-initiated autophagy related phagocytosis. PLoS Pathog. 2016;12(1):e1005363.
  • Bonilla DL, Bhattacharya A, Sha Y, et al. Autophagy regulates phagocytosis by modulating the expression of scavenger receptors. Immunity. 2013;39(3):537–547.
  • Komatsu M, Waguri S, Ueno T, et al. Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J Cell Biol. 2005;169(3):425–434.
  • Pu Q, Gan C, Li R, et al. Atg7 deficiency intensifies inflammasome activation and pyroptosis in Pseudomonas sepsis. J Immunol. 2017;198(8):3205–3213.
  • Ye Y, Li X, Wang W, et al. Atg7 deficiency impairs host defense against Klebsiella pneumoniae by impacting bacterial clearance, survival and inflammatory responses in mice. Am J Physiol Lung Cell Mol Physiol. 2014;307(5):L355–L363.
  • Yang PY, Chen WX, Chang FY, et al. Hepg2 cells infected with Klebsiella pneumoniae show DNA laddering at apoptotic and necrotic stages. Apoptosis. 2012;17(2):154–163.
  • Wang Z, Ren J, Liu Q, et al. Hypermucoviscous Klebsiella pneumoniae infections induce platelet aggregation and apoptosis and inhibit maturation of megakaryocytes. Thromb Res. 2018;171:45–54.
  • Cheng J, Zhang J, Han B, et al. Klebsiella pneumoniae isolated from bovine mastitis is cytopathogenic for bovine mammary epithelial cells. J Dairy Sci. 2020;103(4):3493–3504.
  • Kobayashi SD, Porter AR, Dorward DW, et al. Phagocytosis and killing of Carbapenem-resistant ST258 Klebsiella pneumoniae by human neutrophils. J Infect Dis. 2016;213(10):1615–1622.
  • Lee CH, Chuah SK, Tai WC, et al. Delay in human neutrophil constitutive apoptosis after infection with Klebsiella pneumoniae serotype K1. Front Cell Infect Microbiol. 2017;7:87.
  • Fernandez-Boyanapalli R, McPhillips KA, Frasch SC, et al. Impaired phagocytosis of apoptotic cells by macrophages in chronic granulomatous disease is reversed by IFN-gamma in a nitric oxide-dependent manner. J Immunol. 2010;185(7):4030–4041.
  • Jondle CN, Gupta K, Mishra BB, et al. Klebsiella pneumoniae infection of murine neutrophils impairs their efferocytic clearance by modulating cell death machinery. PLoS Pathog. 2018;14(10):e1007338.
  • Ahn D, Prince A. Participation of necroptosis in the host response to acute bacterial pneumonia. J Innate Immun. 2017;9(3):262–270.
  • Shi J, Zhao Y, Wang K, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 2015;526(7575):660–665.
  • Martinon F, Tschopp J. Inflammatory caspases and inflammasomes: master switches of inflammation. Cell Death Differ. 2007;14(1):10–22.
  • Fernandes-Alnemri T, Wu J, Yu JW, et al. The pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation. Cell Death Differ. 2007;14(9):1590–1604.
  • Ting JP, Willingham SB, Bergstralh DT. NLRs at the intersection of cell death and immunity. Nat Rev Immunol. 2008;8(5):372–379.
  • Hua KF, Yang FL, Chiu HW, et al. Capsular polysaccharide Is involved in NLRP3 inflammasome activation by Klebsiella pneumoniae serotype K1. Infect Immun. 2015;83(9):3396–3409.
  • Cai S, Batra S, Wakamatsu N, et al. NLRC4 inflammasome-mediated production of IL-1beta modulates mucosal immunity in the lung against gram-negative bacterial infection. J Immunol. 2012;188(11):5623–5635.
  • Wang J, Shao Y, Wang W, et al. Caspase-11 deficiency impairs neutrophil recruitment and bacterial clearance in the early stage of pulmonary Klebsiella pneumoniae infection. Int J Med Microbiol: IJMM. 2017;307(8):490–496.
  • Codo AC, Saraiva AC, Dos Santos LL, et al. Inhibition of inflammasome activation by a clinical strain of Klebsiella pneumoniae impairs efferocytosis and leads to bacterial dissemination. Cell Death Dis. 2018;9(12):1182.
  • Ramesh G, MacLean AG, Philipp MT. Cytokines and chemokines at the crossroads of neuroinflammation, neurodegeneration, and neuropathic pain. Mediat Inflamm. 2013;2013:480739.
  • Chen SC, Mehrad B, Deng JC, et al. Impaired pulmonary host defense in mice lacking expression of the CXC chemokine lungkine. J Immunol. 2001;166(5):3362–3368.
  • Lindell DM, Standiford TJ, Mancuso P, et al. Macrophage inflammatory protein 1alpha/CCL3 is required for clearance of an acute Klebsiella pneumoniae pulmonary infection. Infect Immun. 2001;69(10):6364–6369.
  • Zeng X, Moore TA, Newstead MW, et al. Intrapulmonary expression of macrophage inflammatory protein 1alpha (CCL3) induces neutrophil and NK cell accumulation and stimulates innate immunity in murine bacterial pneumonia. Infect Immun. 2003;71(3):1306–1315.
  • Tsai WC, Strieter RM, Wilkowski JM, et al. Lung-specific transgenic expression of KC enhances resistance to Klebsiella pneumoniae in mice. J Immunol. 1998 Sep 1;161(5):2435–2440.
  • Cai S, Batra S, Lira SA, et al. CXCL1 regulates pulmonary host defense to Klebsiella infection via CXCL2, CXCL5, NF-kappaB, and MAPKs. J Immunol. 2010;185(10):6214–6225.
  • Hoffmann E, Dittrich-Breiholz O, Holtmann H, et al. Multiple control of interleukin-8 gene expression. J Leukocyte Biol. 2002;72(5):847–855.
  • Gabellini C, Trisciuoglio D, Desideri M, et al. Functional activity of CXCL8 receptors, CXCR1 and CXCR2, on human malignant melanoma progression. Eur J Cancer. 2009;45(14):2618–2627.
  • Frank CG, Reguerio V, Rother M, et al. Klebsiella pneumoniae targets an EGF receptor-dependent pathway to subvert inflammation. Cell Microbiol. 2013;15(7):1212–1233.
  • Moore TA, Lau HY, Cogen AL, et al. Defective innate antibacterial host responses during murine Klebsiella pneumoniae bacteremia: tumor necrosis factor (TNF) receptor 1 deficiency versus therapy with anti-TNF-alpha. Clin Infect Dis. 2005;41(Suppl 3):S213–S217.
  • Laichalk LL, Kunkel SL, Strieter RM, et al. Tumor necrosis factor mediates lung antibacterial host defense in murine Klebsiella pneumonia. Infect Immun. 1996;64(12):5211–5218.
  • de Paula TP, Santos PC, Arifa R, et al. Treatment with atorvastatin provides additional benefits to imipenem in a model of gram-negative pneumonia induced by Klebsiella pneumoniae in mice. Antimicrob Agents Chemother. 2018;62(5):e00764-17.
  • Yang FL, Yang YL, Liao PC, et al. Structure and immunological characterization of the capsular polysaccharide of a pyrogenic liver abscess caused by Klebsiella pneumoniae: activation of macrophages through Toll-like receptor 4. J Biol Chem. 2011;286(24):21041–21051.
  • Jessop F, Buntyn R, Schwarz B, et al. Interferon gamma reprograms host mitochondrial metabolism through inhibition of complex II To control intracellular bacterial replication. Infect Immun. 2020;88(2):e00744-19.
  • Moore TA, Perry ML, Getsoian AG, et al. Divergent role of gamma interferon in a murine model of pulmonary versus systemic Klebsiella pneumoniae infection. Infect Immun. 2002;70(11):6310–6318.
  • Yoshida K, Matsumoto T, Tateda K, et al. Protection against pulmonary infection with Klebsiella pneumoniae in mice by interferon-gamma through activation of phagocytic cells and stimulation of production of other cytokines. J Med Microbiol. 2001;50(11):959–964.
  • Van Elssen CH, Vanderlocht J, Frings PW, et al. Klebsiella pneumoniae-triggered DC recruit human NK cells in a CCR5-dependent manner leading to increased CCL19-responsiveness and activation of NK cells. Eur J Immunol. 2010;40(11):3138–3149.
  • Ivin M, Dumigan A, de Vasconcelos FN, et al. Natural killer cell-intrinsic type I IFN signaling controls Klebsiella pneumoniae growth during lung infection. PLoS Pathog. 2017;13(11):e1006696.
  • Happel KI, Dubin PJ, Zheng M, et al. Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae. J Exp Med. 2005;202(6):761–769.
  • Greenberger MJ, Kunkel SL, Strieter RM, et al. IL-12 gene therapy protects mice in lethal Klebsiella pneumonia. J Immunol. 1996 Oct 1;157(7):3006–3012.
  • Deng JC, Zeng X, Newstead M, et al. STAT4 is a critical mediator of early innate immune responses against pulmonary Klebsiella infection. J Immunol. 2004;173(6):4075–4083.
  • Bacon CM, Petricoin EF, Ortaldo JR, et al. Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes. Proc Natl Acad Sci U S A. 1995;92(16):7307–7311.
  • Ye P, Rodriguez FH, Kanaly S, et al. Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J Exp Med. 2001;194(4):519–527.
  • Ye P, Garvey PB, Zhang P, et al. Interleukin-17 and lung host defense against Klebsiella pneumoniae infection. Am J Respir Cell Mol Biol. 2001;25(3):335–340.
  • Chen K, Eddens T, Trevejo-Nunez G, et al. IL-17 Receptor signaling in the lung epithelium is required for mucosal chemokine gradients and pulmonary host defense against K. pneumoniae. Cell Host Microbe. 2016;20(5):596–605.
  • Happel KI, Zheng M, Young E, et al. Cutting edge: roles of Toll-like receptor 4 and IL-23 in IL-17 expression in response to Klebsiella pneumoniae infection. J Immunol. 2003;170(9):4432–4436.
  • Happel KI, Odden AR, Zhang P, et al. Acute alcohol intoxication suppresses the interleukin 23 response to Klebsiella pneumoniae infection. Alcohol Clin Exp Res. 2006;30(7):1200–1207.
  • Bloodworth MH, Newcomb DC, Dulek DE, et al. STAT6 signaling attenuates interleukin-17-producing gammadelta T cells during acute Klebsiella pneumoniae infection. Infect Immun. 2016;84(5):1548–1555.
  • Greenberger MJ, Strieter RM, Kunkel SL, et al. Neutralization of IL-10 increases survival in a murine model of Klebsiella pneumonia. J Immunol. 1995 Jul 15;155(2):722–729.
  • Dolgachev VA, Yu B, Sun L, et al. Interleukin 10 overexpression alters survival in the setting of gram-negative pneumonia following lung contusion. Shock. 2014;41(4):301–310.
  • Penaloza HF, Noguera LP, Ahn D, et al. Interleukin-10 produced by myeloid-derived suppressor cells provides protection to carbapenem-resistant Klebsiella pneumoniae sequence type 258 by enhancing Its clearance in the airways. Infect Immun. 2019;87(5):e00665-18.
  • Poe SL, Arora M, Oriss TB, et al. STAT1-regulated lung MDSC-like cells produce IL-10 and efferocytose apoptotic neutrophils with relevance in resolution of bacterial pneumonia. Mucosal Immunol. 2013;6(1):189–199.
  • Chakraborty K, Raundhal M, Chen BB, et al. The mito-DAMP cardiolipin blocks IL-10 production causing persistent inflammation during bacterial pneumonia. Nat Commun. 2017;8:13944.
  • Feriotti C, Sa-Pessoa J, Calderon-Gonzalez R, et al. Klebsiella pneumoniae hijacks the Toll-IL-1R protein SARM1 in a type I IFN-dependent manner to antagonize host immunity. Cell Rep. 2022;40(6):111167.
  • Ahn D, Wickersham M, Riquelme S, et al. The effects of IFN-lambda on epithelial barrier function contribute to Klebsiella pneumoniae ST258 Pneumonia. Am J Respir Cell Mol Biol. 2019;60(2):158–166.
  • Ahn D, Prince A. Participation of the IL-10RB related cytokines, IL-22 and IFN-lambda in defense of the airway mucosal barrier. Front Cellular Infect Microbiol. 2020;10:300.
  • Aujla SJ, Chan YR, Zheng M, et al. IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat Med. 2008;14(3):275–281.
  • Zheng M, Horne W, McAleer JP, et al. Therapeutic role of interleukin 22 in experimental intra-abdominal Klebsiella pneumoniae infection in mice. Infect Immun. 2016;84(3):782–789.
  • Ali S, Alam M, Hasan GM, et al. Potential therapeutic targets of Klebsiella pneumoniae: a multi-omics review perspective. Brief Funct Genomics. 2022;21(2):63–77.
  • A MS NVV, et al AIB. Characterization and therapeutic potential of bacteriophage-encoded polysaccharide depolymerases with beta galactosidase activity against Klebsiella pneumoniae K57 Capsular Type. Antibiotics. 2020 Oct 25;9(11):732.
  • de Souza CM, da Silva AP, Junior NGO, et al. Peptides as a therapeutic strategy against Klebsiella pneumoniae. Trends Pharmacol Sci. 2022;43(4):335–348.
  • Standiford LR, Standiford TJ, Newstead MJ, et al. TLR4-dependent GM-CSF protects against lung injury in gram-negative bacterial pneumonia. Am J Physiol Lung Cellular Mol Physiol. 2012;302(5):L447–L454.
  • Iwanaga N, Sandquist I, Wanek A, et al. Host immunology and rational immunotherapy for carbapenem-resistant Klebsiella pneumoniae infection. JCI Insight. 2020;5(8):e135591.
  • Ding J, Liu Q. Toll-like receptor 4: A promising therapeutic target for pneumonia caused by Gram-negative bacteria. J Cell Mol Med. 2019;23(9):5868–5875.
  • Muller-Redetzky H, Lienau J, Suttorp N, et al. Therapeutic strategies in pneumonia: going beyond antibiotics. Eur Resp Rev. 2015;24(137):516–524.