Gut microbiota-reactive IgG regulates gut microbiota development and immunity against enteric pathogens in early life

Abstract

Abstract The gut microbiota elicits antigen-specific IgG at steady state that cross-reacts to pathogenic Gram-negative Enterobacteriaceae to confer protection against systemic infection. The role of these IgG antibodies in the development of gut microbiome and immunity against enteric pathogens in early life, however, remains largely undefined. In this study, we demonstrate that gut microbiota-induced maternal IgG is transferred to the neonatal gut through maternal milk via the neonatal Fc receptor and confers critical protection by inhibiting colonization and attachment of C. rodentium to the mucosa in the neonatal gut. Enhanced neonatal immunity against oral C. rodentium infection was observed following maternal immunization with a gut microbiota-derived IgG antigen, outer-membrane protein A (OMP-A), or induction of protective IgG antibodies in germ-free mice after reconstitution with IgG-inducing gut bacteria. Furthermore, we generated a mouse model with complete deficiency in all IgG isotypes. IgG-deficient neonatal mice exhibited increased susceptibility to C. rodentium infection, altered gut microbiome and increased numbers of intestinal IL-17-producing γδ T cells driven by the gut microbiome at steady state. The altered gut microbiome persisted into adulthood in IgG KO mice and contributed to increased disease severity in DSS-induced colitis. Taken together, our studies have defined critical roles for gut microbiome-induced IgG antibodies in shaping the gut microbiome and immunity against Gram-negative enteric pathogens from early life to adulthood.