No abstract

BackgroundIL-17 and IL-22 cytokines play an important role in protective immune responses against Mycobacterium tuberculosis (Mtb) infection. Information on the production of these cytokines and the factors that regulate their production in the context of human immunodeficiency virus (HIV) and latent tuberculosis infection (LTBI) or active tuberculosis disease (ATB) is limited. In the current study, we compared the production of these two cytokines by PBMC of HIV-LTBI+ and HIV + LTBI+ individuals in response to Mtb antigens CFP-10 (culture filtrate protein) and ESAT-6 (Early Secretory Antigenic Target). We also determined the mechanisms involved in their production.MethodsWe cultured Peripheral Blood Mononuclear Cells (PBMCs) from HIV- individuals and HIV+ patients with latent tuberculosis and active disease with CFP-10 and ESAT-6. Production of IL-17, IL-22 and PD1 (Programmed Death 1), ICOS (Inducible T-cell Costimulator), IL-23R and FoxP3 (Forkhead box P3) expression on CD4+ T cells was measured.ResultsIn response to Mtb antigens CFP-10 and ESAT-6, freshly isolated PBMCs from HIV+ LTBI+ and HIV+ active TB patients produced less IL-17 and IL-22 and more IL-10, expressed less IL-23R, and more PD1 and expanded to more FoxP3+ cells. Active TB infection in HIV+ individuals further inhibited antigen specific IL-17 and IL-22 production compared to those with LTBI. Neutralization of PD1 restored IL-23R expression, IL-17 and IL-22 levels and lowered IL-10 production and reduced expansion of FoxP3 T cells.ConclusionsIn the current study we found that increased PD1 expression in HIV + LTBI+ and HIV+ active TB patients inhibits IL-17, IL-22 production and IL-23R expression in response to Mtb antigens CFP-10 and ESAT-6.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3236-0) contains supplementary material, which is available to authorized users.

These findings suggest that activated T cells enhance NK cell responses to lyse Mtb-infected human monocytes and restrict Mtb growth in monocytes through IL-21 production. Interleukin-21-activated NK cells also enhance the immune response by augmenting IL-1β, IL-18, and MIP-1β production and reducing IL-10 production by monocytes in response to an intracellular pathogen.