Astrovirus infection dysregulates goblet cell-associated antigen passages

Abstract

Summary Astroviruses are a major cause of pediatric diarrhea worldwide. Goblet cells are a primary target for astrovirus infection. In addition to secreting mucus, goblet cells facilitate oral tolerance through the formation of goblet cell-associated antigen passages (GAPs). Previous work showed that GAPs close in response to Salmonella infection to minimize its dissemination and prevent inappropriate inflammatory responses to dietary antigens. In contrast, we observed that GAPs remain open following astrovirus infection, likely due to the downregulation of epidermal growth factor receptor that mediates GAP closure. Further, Salmonella-induced GAP closure was reduced by astrovirus co-infection, and we observed higher bacterial dissemination in co-infected animals. Together, our study indicates that astrovirus-infected goblet cells are refractory to GAP inhibition, which impairs the protective host responses that combat a co-infecting bacterial pathogen.