Loss of circulating CD8α + NK cells during human Mycobacterium tuberculosis infection.

Autor:	Mehanna N; Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, 11794., Pradhan A; Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, 11794., Kaur R; Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, 11794., Kontopoulos T; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Rosati B; Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, 11794., Carlson D; Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, 11794., Cheung NK; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Xu H; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Bean J; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Hsu K; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Le Luduec JB; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Vorkas CK; Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, 11794.; Department of Microbiology and Immunology, Stony Brook University, Stony Brook, NY 11794.; Center for Infectious Diseases, Stony Brook University, Stony Brook, NY, 11794.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 May 13. Date of Electronic Publication: 2024 May 13.
DOI:	10.1101/2024.04.16.588542
Abstrakt:	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 CD8α 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 CD8α + NK cells demonstrated enhanced maturity, cytotoxic gene expression, and response to cytokine stimulation relative to CD8α - NK cells. CD8α + 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 CD8α + NK cell populations during Mtb infection correlating with disease resistance. Competing Interests: Competing interests: Authors declare that they have no competing interests.
Databáze:	MEDLINE
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