HIV Skews a balanced Mtb-specific Th17 response in latent tuberculosis subjects to a pro-inflammatory profile independent of viral load

Rakshit, S.; Hingankar, N.; Alampalli, S.V.; Adiga, V.; Sundararaj, B.K.; Sahoo, P.N.; ... ; Vyakarnam, A. (2020)

Article / Letter to editor

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)-gamma(+)/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.

• All authors: Rakshit, S.; Hingankar, N.; Alampalli, S.V.; Adiga, V.; Sundararaj, B.K.; Sahoo, P.N.; Finak, G.; Kumar, J.A.J.U.; Dhar, C.; D'Souza, G.; Virkar, R.G.; Ghate, M.; Thakar, M.R.; Paranjape, R.S.; Rosa, S.C. de; Ottenhoff, T.H.M.; Vyakarnam, A.
• Date: 2020-12-01
• Journal: Cell Reports
• Volume: 33
• Issue: 9
• DOI: doi:10.1016/j.celrep.2020.108451
• Link: https://www.sciencedirect.com/science/article/pii/S2211124720314406?via%...