Mucosal Immunol. 2025 Sep 18:S1933-0219(25)00094-7. doi: 10.1016/j.mucimm.2025.09.004. Online ahead of print.
ABSTRACT
Mucosal IgA antibodies are the first defence against mucosal infections. Besides targeting specific antigens by their Fab-region, IgA also mediates antiviral functions via their Fc-domain, allowing infected cells destruction by antibody-dependent cellular phagocytosis (ADCP). Passive immunisation with anti-HIV-1 IgG protected Non-Human Primates in a CD8+ T cell-dependent manner, a process likely involving ADCP. Here, we unravel the consequences of ADCP of HIV-1-infected cells mediated by anti-HIV envelope IgA compared to IgG. We found that IgA-mediated ADCP, not IgG, drives viral antigen cross-presentation to HIV-1-specific cytotoxic CD8+ T cells. IgA effector function reprogrammed ADCP effector monocytes into activated macrophages exhibiting a mixed pro- and anti-inflammatory profile combined with increased pro-inflammatory chemokines. IgA-mediated ADCP sensitizes monocytes to respond to a novel bacterial challenge by secreting IL-6 and TNFα, indicative of acquired trained immunity. Altogether, these data establish a bridge between humoral and cellular immunity that could be exploited in HIV preventive strategies.
PMID:40975322 | DOI:10.1016/j.mucimm.2025.09.004