HIV Skews a Balanced Mtb-Specific Th17 Response in Latent Tuberculosis Subjects to a Pro-inflammatory Profile Independent of Viral Load.

Autor:	Rakshit S; Laboratory of Immunology of HIV-TB Co-infection, Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India., Hingankar N; Laboratory of Immunology of HIV-TB Co-infection, Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India., Alampalli SV; Laboratory of Immunology of HIV-TB Co-infection, Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India., Adiga V; Laboratory of Immunology of HIV-TB Co-infection, Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India., Sundararaj BK; Laboratory of Immunology of HIV-TB Co-infection, Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India., Sahoo PN; Laboratory of Immunology of HIV-TB Co-infection, Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India., Finak G; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Uday Kumar J AJ; Departments of Infectious Diseases & Pulmonary Medicine, St. John's Research Institute, Bangalore, India., Dhar C; Departments of Infectious Diseases & Pulmonary Medicine, St. John's Research Institute, Bangalore, India., D'Souza G; Departments of Infectious Diseases & Pulmonary Medicine, St. John's Research Institute, Bangalore, India., Virkar RG; National Aids Research Institute, Bhosari, Pune, Maharashtra, India., Ghate M; National Aids Research Institute, Bhosari, Pune, Maharashtra, India., Thakar MR; National Aids Research Institute, Bhosari, Pune, Maharashtra, India., Paranjape RS; National Aids Research Institute, Bhosari, Pune, Maharashtra, India., De Rosa SC; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Ottenhoff THM; Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands., Vyakarnam A; Laboratory of Immunology of HIV-TB Co-infection, Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India; Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, Faculty of Life Sciences & Medicine, Guy's Hospital, King's College London, London SE1 9RT, UK. Electronic address: anna.vyakarnam@kcl.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2020 Dec 01; Vol. 33 (9), pp. 108451.
DOI:	10.1016/j.celrep.2020.108451
Abstrakt:	HIV infection predisposes latent tuberculosis-infected (LTBI) subjects to active TB. This study is designed to determine whether HIV infection of LTBI subjects compromises the balanced Mycobacterium tuberculosis (Mtb)-specific T helper 17 (Th17) response of recognized importance in anti-TB immunity. Comparative analysis of Mtb- and cytomegalovirus (CMV)-specific CD4 + T cell responses demonstrates a marked dampening of the Mtb-specific CD4 + T cell effectors and polyfunctional cells while preserving CMV-specific response. Additionally, HIV skews the Mtb-specific Th17 response in chronic HIV-infected LTBI progressors, but not long-term non-progressors (LTNPs), with preservation of pro-inflammatory interferon (IFN)-γ + /interleukin-17 + (IL-17 + ) and significant loss of anti-inflammatory IL-10 + /IL-17 + effectors that is restored by anti-retroviral therapy (ART). HIV-driven impairment of Mtb-specific response cannot be attributed to preferential infection as cell-associated HIV DNA and HIV RNA reveal equivalent viral burden in CD4 + T cells from different antigen specificities. We therefore propose that beyond HIV-induced loss of Mtb-specific CD4 + T cells, the associated dysregulation of Mtb-specific T cell homeostasis can potentially enhance the onset of TB in LTBI subjects. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020. Published by Elsevier Inc.)
Databáze:	MEDLINE
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