Monocyte-Derived IL-5 Reduces TNF Production by Mycobacterium tuberculosis –specific CD4 T Cells during SIV/ M. tuberculosis Coinfection

Abstract

HIV-infected individuals are significantly more susceptible to tuberculosis (TB) than uninfected individuals. Although it is established that HIV reduces Mycobacterium tuberculosis–specific T cell responses, the causes of this dysfunction are not known. We used the cynomolgus macaque model of TB to demonstrate that ex vivo SIV reduces the frequency of M. tuberculosis–specific TNF and IFN-γ–producing T cells within 24 h after infection. In vivo, T cell IFN-γ responses in granulomas from animals with SIV/M. tuberculosis coinfection were lower than SIV-negative animals with active TB. The SIV effects on the inhibition of T cell responses were primarily on APCs and not the T cells directly. Specifically, reductions in the frequency of TNF-producing M. tuberculosis–specific CD4 T cells were caused, at least in part, by SIV-induced production of monocyte derived IL-5.