High-parameter phenotypic characterization reveals a subset of human Th17 cells that preferentially produce IL17 against M. tuberculosis antigen.

Autor:	Ogongo P; Division of Experimental Medicine, University of California, San Francisco, CA, USA.; Department of Tropical and Infectious Diseases, Institute of Primate Research, Nairobi, Kenya., Tran A; Division of Experimental Medicine, University of California, San Francisco, CA, USA., Marzan F; Drug Research Unit, Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, CA, USA., Gingrich D; Drug Research Unit, Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, CA, USA., Krone M; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA., Aweeka F; Drug Research Unit, Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, CA, USA., Lindestam Arlehamn CS; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA., Martin JN; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA., Deeks SG; Division of HIV, Infectious Diseases, and Global Medicine, University of California, San Francisco, CA, USA., Hunt PW; Division of Experimental Medicine, University of California, San Francisco, CA, USA., Ernst JD; Division of Experimental Medicine, University of California, San Francisco, CA, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Mar 06. Date of Electronic Publication: 2024 Mar 06.
DOI:	10.1101/2023.01.06.523027
Abstrakt:	Background: Interleukin 17 producing CD4 T cells contribute to the control of Mycobacterium tuberculosis (Mtb) infection in humans; whether infection with Human Immunodeficiency Virus (HIV) disproportionately affects distinct Th17 cell subsets that respond to Mtb is incompletely defined. Methods: We performed high-definition characterization of circulating Mtb -specific Th17 cells by spectral flow cytometry in people with latent TB and treated HIV (HIV-ART). We also measured kynurenine pathway activity by LC/MS on plasma and tested the hypothesis that tryptophan catabolism influences Th17 cell frequencies in this context. Results: We identified two subsets of Th17 cells: subset 1 defined as CD4 + Vα7.2 - CD161 + CD26 + and subset 2 defined as CD4 + Vα7.2 - CCR6 + CXCR3 - cells of which subset 1 was significantly reduced in LTBI with HIV-ART, yet Mtb -responsive IL17-producing CD4 T cells were preserved; we found that IL17-producing CD4 T cells dominate the response to Mtb antigen but not CMV antigen or staphylococcal enterotoxin B (SEB); and tryptophan catabolism negatively correlates with both subset 1 and subset 2 Th17 cell frequencies. Conclusions: We found differential effects of ART-suppressed HIV on distinct subsets of Th17 cells, that IL17-producing CD4 T cells dominate responses to Mtb but not CMV antigen or SEB, and that kynurenine pathway activity is associated with decreases of circulating Th17 cells that may contribute to tuberculosis immunity. Competing Interests: Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Databáze:	MEDLINE
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