Rakshit, S and Hingankar, N and Alampalli, SV and Adiga, V and Sundararaj, BK and Sahoo, PN and Finak, G and Uday Kumar J, AJ and Dhar, C and D'Souza, G and Virkar, RG and Ghate, M and Thakar, MR and Paranjape, RS and De Rosa, SC and Ottenhoff, THM and Vyakarnam, A (2020) HIV Skews a Balanced Mtb-Specific Th17 Response in Latent Tuberculosis Subjects to a Pro-inflammatory Profile Independent of Viral Load. In: Cell Reports, 33 (9).
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Abstract
This study provides insight on how HIV may drive tuberculosis (TB). Rakshit et al. demonstrate that HIV infection of latent TB subjects profoundly alters specific immune subsets implicated in anti-TB immunity, which is independent of cellular viral burden or secretion of antiviral chemokines. © 2020 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. © 2020
| Item Type: | Journal Article |
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| Publication: | Cell Reports |
| Publisher: | Elsevier B.V. |
| Additional Information: | The copyright for this article belongs to the Author(s). |
| Keywords: | gamma interferon; helper factor; interleukin 10; interleukin 17; macrophage inflammatory protein 1beta; virus DNA; virus RNA; IL17A protein, human, adult; antigen specificity; antiretroviral therapy; Article; bacterial immunity; CD4+ T lymphocyte; clinical article; cohort analysis; controlled study; cytokine production; Cytomegalovirus; disease exacerbation; female; gene expression regulation; human; Human immunodeficiency virus infection; infection control; latent tuberculosis; male; Mycobacterium tuberculosis; priority journal; protein depletion; T lymphocyte; virus load; complication; genetics; Human immunodeficiency virus infection; latent tuberculosis; metabolism; procedures; virus load; young adult, Adult; Female; HIV Infections; Humans; Interleukin-17; Latent Tuberculosis; Male; Viral Load; Young Adult |
| Department/Centre: | Division of Biological Sciences > Centre for Infectious Disease Research |
| Date Deposited: | 10 Jan 2023 05:23 |
| Last Modified: | 10 Jan 2023 05:23 |
| URI: | https://eprints.iisc.ac.in/id/eprint/78976 |
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