Loss of circulating CD8α+ NK cells during human Mycobacterium tuberculosis infection
Mehanna, N.; Pradhan, A.; Kaur, R.; Kontopoulos, T.; Rosati, B.; Carlson, D.; Cheung, N.-K.; Xu, H.; Bean, J.; Hsu, K.; Le Luduec, J.-B.; Vorkas, C. K.
Show abstract
Natural Killer (NK) cells can recognize and kill Mtb-infected cells in vitro, however their role after natural human exposure has not been well-studied. To identify Mtb-responsive NK cell populations, we analyzed the peripheral blood of healthy household contacts of active Tuberculosis (TB) cases and source community donors in an endemic region of Port-au-Prince, Haiti by flow cytometry. We observed higher CD8 expression on NK cells in putative resistors (IGRA-contacts) with a progressive loss of these circulating cells during household-associated latent infection and disease. In vitro assays and CITE-seq analysis of CD8+ NK cells demonstrated enhanced maturity, cytotoxic gene expression, and response to cytokine stimulation relative to CD8- NK cells. CD8+ NK cells also displayed dynamic surface expression dependent on MHC I in contrast to conventional CD8+ T cells. Together, these results support a specialized role for CD8+ NK cell populations during Mtb infection correlating with disease resistance.
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