Tuberculosis-driven heterologous immunity to HIV-1 and consequences in HIV-1 co-infection
Embargo Date
2025-11-02
OA Version
Citation
Abstract
Mycobacterium tuberculosis (Mtb) is proven to augment protection against unrelated pathogens through enhanced antibody responses and epigenetic remodeling of innate immune cells. Although the role of Mtb on HIV-1 specific antibody responses has not been explored, the recognition of highly immunogenic antigens on Mtb may trigger a cascade of events culminating in an increased HIV-1 antigen presentation and specific B cell responses. Here, we compared HIV-1-specific antibody responses among people with HIV-1 either with or without active Mtb and simulated immune responses to HIV-1 infection and Mtb antigens using a tonsil organoid model.
We examined HIV-1 specific neutralization and antibody-dependent cellular cytotoxicity (ADCC) breadth and potency (BP) among people with HIV-1 either with or without active Mtb (PWH/Active Mtb, PWH/Treated Mtb, and PWH/No Mtb). Before antiretroviral treatment (ART) and Mtb treatment, PWH/Active Mtb as compared to PWH/No Mtb demonstrated higher neutralization BP. During ART, PWH who developed new Mtb disease (PWH/Active Mtb) as compared to PWH/Treated Mtb and PWH/No Mtb had the highest fold increase in neutralization and ADCC BP. Neutralization BP did not associate with previously described determinants like HIV-1 virus levels, envelope diversity, and IgG concentrations, but associated with B cell cytokines (BAFF, APRIL, and IL-6) and ADCC BP. Our data suggest that active Mtb is associated with the augmentation of HIV-1 specific B cell responses before and during ART.
Broad and potent anti-HIV-1 antibodies emerge from the germinal center activity in the lymph node. Mtb disease potentially exerts a bystander effect through cytokines on HIV-1 specific B and T cells. Additionally, Mtb disease may be broadening B cell responses by enhancing HIV-1 envelope expression. We used Mtb-derived antigens to simulate Mtb co-infection in HIV-1 infected human tonsils. HIV-1 infected as compared to HIV-1 infected and Mtb-antigen stimulated tonsil organoids had similar proportions of B and T cell subsets over 1 week in culture. HIV-1 infection led to the loss of CD4 T and T follicular helper cells in both groups. The tonsil organoid model may allow us to explore mechanisms underlying Mtb mediated enhancement of HIV-1 specific antibody responses in future studies.