Tuberculosis distorts the inhibitory impact of interleukin-10 in HIV infection

Objectives: This study aimed to assess how Mycobacterium tuberculosis (MTB) coinfection alters the impact of interleukin-10 in chronic HIV infection. Design: We assessed plasma cytokine levels (interleukin-10, interferon-γ, tumor necrosis factor-γ, interleukin-2, interleukin-6 and interleukin-13) in 82 individuals presenting with HIV monoinfection, HIV-LTBI (latent MTB infection) coinfection or HIV-TB (active tuberculosis) coinfection. We also assessed the influence of MTB on the functional impact of interleukin-10 receptor alpha (interleukin-10Ra) blockade on HIV and MTB-specific CD4+ T cells. Methods: Plasma cytokine levels were measured by high sensitivity Luminex. We used an ex-vivo interleukin-10Ra blockade assay to assess if functional enhancement of HIV and MTB-specific CD4+ T cells was possible following a 48-h stimulation with HIV gag or pooled ESAT-6 (6 kDa early secretory antigenic target) and CFP-10 (10-kDa culture filtrate protein) peptides. Cell supernatant was collected 48 h after stimulation and the cytokine profile was measured by Luminex. Results: Plasma interleukin-10 levels were elevated in HIV-TB as compared with HIV monoinfection (P<0.05) and HIV-LTBI (P<0.05). Plasma interleukin-10 levels correlated to HIV viral load in HIV monoinfection (P=0.016) and HIV-LTBI (P=0.042), but not HIV-TB. Ex-vivo blockade of interleukin-10Ra significantly enhanced MTB and HIVspecific CD4+ T-cell function in HIV-LTBI individuals but not in HIV-TB individuals. Conclusion: Tuberculosis disrupts the correlation between interleukin-10 and markers of HIV disease progression. In addition, HIV-TB is associated with a more inflammatory cytokine milieu compared with HIV monoinfection. Interestingly, interleukin-10Ra blockade can enhance both HIV and MTB-specific T-cell function in HIV-LTBI, but not in HIV-TB coinfection.