Platelet-derived major histocompatibility complex class I coating on Treponema pallidum attenuates natural killer cell lethality

ABSTRACT

The evasive tactics of Treponema pallidum pose a major challenge in combating and eradicating syphilis. Natural killer (NK) cells mediate important effector functions in the control of pathogenic infection, preferentially eliminating targets with low or no expression of major histocompatibility complex (MHC) class I. To clarify T. pallidum’s mechanisms in evading NK-mediated immunosurveillance, experiments were performed to explore the cross-talk relations among T. pallidum, NK cells, and platelets. T. pallidum adhered to, activated, and promoted particle secretion of platelets. After preincubation with T. pallidum, platelets expressed and secreted high levels of MHC class I, subsequently transferring them to the surface of T. pallidum, potentially inducing an immune phenotype characterized by the “pseudo-expression” of MHC class I on the surface of T. pallidum (hereafter referred to a “pseudo-expression” of MHC class I). The polA mRNA assay showed that platelet-preincubated T. pallidum group exhibited a significantly higher copy number of polA transcript than the T. pallidum group. The survival rate of T. pallidum mirrored that of polA mRNA, indicating that preincubation of T. pallidum with platelets attenuated NK cell lethality. Platelets pseudo-expressed the MHC class I ligand on the T. pallidum surface, facilitating binding to killer cell immunoglobulin-like receptors with two immunoglobulin domains and long cytoplasmic tail 3 (KIR2DL3) on NK cells and initiating dephosphorylation of Vav1 and phosphorylation of Crk, ultimately attenuating NK cell lethality. Our findings elucidate the mechanism by which platelets transfer MHC class I to the T. pallidum surface to evade NK cell immune clearance.

KEYWORDS:

• Immunosurveillance
• natural killer cells
• MHC class I
• platelets
• Treponema pallidum

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data Availability statement

The authors confirm that the data supporting the findings of this study are available within the article and/or its supplementary materials.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [grant numbers 81973104, 82272370 to T.-C. Y], the Key projects of the Natural Science Foundation of Fujian Province [grant number 2021J02055 to T.-C. Y.]; the Xiamen Science and Technology Planning Project [grant number 3502Z20224036 to T.-C. Y.]; the Natural Science Foundation of Fujian Province, China [grant number 2021J01073 to M.-L. T., grant number 2022J011346 to D. L.] and the Youth Fund of the National Natural Science Foundation of China [grant number 82001292 to D. L.]. The funders played no role in the study design, data collection or analyses, the decision to publish, or manuscript preparation.