Exploration of the pathogenesis of HIV/Mtb co-infection based on SOCS1-TLR2 signaling pathway

Objective: To investigate the role of suppressor of cytokine signaling 1(SOCS1)-toll-like receptor 2(TLR2) signaling pathway in macrophages in the promotion of Mycobacterium tuberculosis(Mtb) infection by human immunodeficiency virus(HIV). Methods: Peripheral venous blood was collected from HIV-1 mono-infection patients, Mtb mono-infection patients, HIV-1/Mtb co-infection patients and healthy controls, and peripheral blood mononuclear cells(PBMCs) were isolated, and the expression levels of SOCS1, TLR2 and downstream Mtb infection-related factors in mononuclear macrophages in PBMCs were detected by flow cytometry. Based on the macrophage-HIV-Mtb infection model, the role of SOCS1-TLR2 in HIV-promoted Mtb infection was explored. Results: Compared with the healthy control group, the protein expression levels of interleukin(IL)-6, IL-10 were increased in the HIV-1 mono-infection group, Mtb mono-infection group and HIV-1/Mtb co-infection group(P<0.05) and the protein expression levels of IL-1β, IL-12 and interferon(IFN)-γ were increased in the Mtb mono-infection group(P<0.05). In vitro cell experiments, compared with the control group, the expression levels of SOCS1 mRNA in the HIV-1 mono-infection group, Mtb mono-infection group and HIV-1/Mtb co-infection group were increased(P<0.05), and the expression levels of TLR2 mRNA in the HIV-1 mono-infection group and HIV-1/Mtb co-infection group were decreased(P<0.05). After constructing an infection group with overexpressed SOCS1, compared with the control group, the expression levels of SOCS1 and IL-6 in the HIV-1 mono-infection group and the HIV-1/Mtb co-infection group were increased(P<0.05) and the expression levels of SOCS1 and IL-6 in the HIV-1/Mtb co-infection group were decreased after the TLR2 agonist was added(P<0.05). HIV/Mtb co-infection group with overexpressed SOCS1 had the highest Mtb colony count(P<0.05). Conclusion: HIV-1 may facilitate Mtb infection by promoting the high expression of inflammatory cytokines IL-6 and IL-10 in the SOCS1-TLR2 signaling pathway.