Name
Investigating the role of M cells in rotavirus immune response
Presenter
Avan Antia, Washington University School of Medicine
Co-Author(s)
Siyuan Ding (Department of Microbiology, Washington University in St. Louis School of Medicine)
Abstract Category
Pathogenesis and Immunity
Abstract
Although most microbial pathogens enter through the host mucosa, the development of mucosal vaccines lags far behind that of injectable vaccines. Unlike injectable vaccines, mucosal vaccines induce mucosal IgA and can thus prevent initial infection and transmission. M cells, located on Peyer’s Patches in the small intestine, facilitate the sampling of bacterial and protein antigen from the lumen and subsequent IgA production. IgA provides sterilizing immunity against certain enteric viruses, including rotavirus (RV). To develop more effective mucosal vaccines, it is crucial to understand the complexities of mucosal immune response and M cell function in the context of enteric viral infections.
In this study, we use RV as a prototypic enteric virus and a conditional M cell knockout mouse model to study their interactions. We found that upon oral vaccination with a low dose of live-attenuated RV, compared to Tnfrsf11afl/fl control mice, M cell-deficient Tnfrsf11afl/fl Villin-Cre mice failed to produce intestinal anti-RV IgA and were susceptible to challenge by a virulent RV strain. However, both groups developed comparable systemic IgG responses, suggesting that M cell-mediated antigen sampling is not critical for systemic humoral response. Additionally, we found that upon oral infection with virulent RV, both M cell knockout and control mice similarly produced robust anti-RV IgA, suggesting that M cells are dispensable when antigens are abundant in the lumen. Collectively, our studies enhance our understanding of the protective role of M cells against enteric virus infection and pave the way for developing improved oral vaccines.
In this study, we use RV as a prototypic enteric virus and a conditional M cell knockout mouse model to study their interactions. We found that upon oral vaccination with a low dose of live-attenuated RV, compared to Tnfrsf11afl/fl control mice, M cell-deficient Tnfrsf11afl/fl Villin-Cre mice failed to produce intestinal anti-RV IgA and were susceptible to challenge by a virulent RV strain. However, both groups developed comparable systemic IgG responses, suggesting that M cell-mediated antigen sampling is not critical for systemic humoral response. Additionally, we found that upon oral infection with virulent RV, both M cell knockout and control mice similarly produced robust anti-RV IgA, suggesting that M cells are dispensable when antigens are abundant in the lumen. Collectively, our studies enhance our understanding of the protective role of M cells against enteric virus infection and pave the way for developing improved oral vaccines.