IgA clears gut viruses

Abstract

Secretory IgA coats the intestinal microbiota and is the most abundant antibody isotype produced in the mammalian gastrointestinal mucosa. In Cell Host and Microbe, Lisicka et al. show that IgA prevents chronic gut colonization by viruses and that IgA deficiency in some individuals increases susceptibility to colitis if exposed to viral pathobionts. The authors designed a mouse model of secretory IgA deficiency to demonstrate that IgA mediates regulation of the microbiota by preventing the expansion of antigen-driven CD8αβ⁺ intraepithelial lymphocytes (IELs) primed by type 1 conventional dendritic cells (cDC1). Using germ-free mice and colonizing them with fecal filtrate from their mouse model, the authors conclude that murine astrovirus (MuAstV) drives CD8αβ⁺ IELs in IgA-deficient mice, which are not able to clear the virus, but can maintain homeostasis. The authors show that IgA derived from the germinal center plasma cells regulates the colonization of specific RNA viruses in the small intestine and limits the expansion of CD8αβ⁺ T cells. Using diverse mouse models for colitis, they conclude that in genetically susceptible mice, IgA deficiency combined with the presence of murine norovirus increases susceptibility to colitis.

Original reference: Cell Host Microbe 33, 498–511.e10 (2025)