AIDS Progression Is Associated with the Emergence of IL-17–Producing Cells Early After Simian Immunodeficiency Virus Infection

Abstract

IL-17 is a potent effector cytokine involved in inflammatory response and antimicrobial defense. We report that SIV infection of rhesus macaques (RMs) results in the emergence of IL-17–expressing cells during the acute phase. This subpopulation appears at day 14 postinfection concomitantly with an increase in TGF-β and IL-18 expression. This subset, which exhibits phenotypic markers of NK T cells (NKT), rather than Th17 CD4 cells, persists during the chronic phase and is higher in noncontrollers SIV-infected RMs compared with controllers SIV-infected RMs. In contrast, in the nonpathogenic model of SIVagm infection of African green monkeys, no change in the level of IL-17–expressing cells is observed in lymphoid organs. Consistent with the emergence of TGF-β and IL-18 during the acute phase in SIV-infected RMs, but not in SIV-infected African green monkeys, we demonstrate that in vitro TGF-β and IL-18 induce the differentiation and expansion of IL-17+NKT+. Altogether, these results demonstrate that IL-17–producing NKT are associated with the pathogenesis of SIV in RMs and suggest that TGF-β and IL-18 play a role in their development.

Neutrophils in antiretroviral therapy–controlled HIV demonstrate hyperactivation associated with a specific IL-17/IL-22 environment

“…48 Furthermore, IL-17 production was higher in the HIV(I) group than in the HIV(NI) group and was positively correlated with basal PMN hyperactivation. IL-17 plays a central role in both host defense and the induction and progression of multiple chronic inflammatory diseases.…”

Lipopolysaccharide Induces Immune Activation and SIV Replication in Rhesus Macaques of Chinese Origin

“…Similar to HIV infection, SIV infection of rhesus macaque could also result in a dramatic and selective loss of memory CD4+ T cells predominately from the mucosal surface in GI tract [22], [23]. This drastic depletion of CD4+ T cells in the intestine was also found in SIV-infected rhesus macaques of China origin [24], [25]. In contrast, SIV infection of natural host primates is associated with no microbial translocation and/or immune activation [17], [26].…”

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

“…However, infection of Treg cells with HIV represses Foxp3 expression, reduces the generation of TGF-b, and increases IL-4 production, thus limiting Treg-cell function (Pion et al 2013) and likely contributing to chronic inflammation seen in HIV-infected patients. TGF-b produced in the mucosal lymph nodes during HIV infection can also induce apoptosis of activated CD8 þ T cells (Cumont et al 2007), whereas promoting the generation of NKT cells, which share properties of both T cells and NK cells, which produce IL-17 (Campillo-Gimenez et al 2010). Furthermore, the HIV envelope protein gp120 can bind to a4b7 integrins on naïve B cells to induce TGF-b and Fc receptor-like 4 (FcRL4) expression, which causes B-cell dysfunction and inhibits their proliferation (Jelicic et al 2013).…”