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. / 2025-11-02T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/47412 |
| Date | 02 November 2023 |
| Creators | Adeoye, Bukola |
| Contributors | Sagar, Manish |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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