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.

doi:10.1101/2024.04.16.588542

bioRxiv · 10.1101/2024.04.16.588542

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.

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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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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.. 2024-04-20. Loss of circulating CD8α+ NK cells during human Mycobacterium tuberculosis infection. https://doi.org/10.1101/2024.04.16.588542

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