IgA Response to Symbiotic Bacteria as a Mediator of Gut Homeostasis

Abstract

Colonization of germ-free mice with a normal gut microbiota elicits bacteria-specific IgA antibody responses. The effects of these responses on microbial and host biology remain poorly defined. Therefore, we developed a gnotobiotic mouse model where the microbiota is reduced to one bacterial species, and the antibody repertoire to a single, monoclonal IgA against the bacterium's capsular polysaccharide. Bacteroides thetaiotaomicron was introduced into germ-free wild-type, immunodeficient Rag1(-/-), or Rag1(-/-) mice harboring IgA-producing hybridoma cells. Without IgA, B. thetaiotaomicron elicits a more robust innate immune response and reacts to this response by inducing genes that metabolize host oxidative products. IgA reduces intestinal proinflammatory signaling and bacterial epitope expression, thereby balancing suppression of the oxidative burst with the antibody's negative impact on bacterial fitness. These results underscore the adaptive immune system's critical role in establishing a sustainable host-microbial relationship. Immunoselection of bacterial epitope expression may contribute to the remarkable strain-level diversity in this ecosystem.

Physiological and biochemical characterization of the two α-l-rhamnosidases of Lactobacillus plantarum NCC245

“…It is known that a-L-Rhamnosidases of L. plantarum some lactobacilli degrade their own EPS structures after prolonged fermentation (Pham et al, 2000), in stationary phase, when a-L-rhamnosidase of L. plantarum NCC245 is the most active. Perpetual modification of the surface polysaccharide structures might also be a strategy of intestinal bacteria to survive the selective pressure of the adaptive immune system of the host and remain an entrenched resident of the community (Peterson et al, 2007). Finally, it is possible that the natural substrate for a-L-rhamnosidases of L. plantarum has not yet been identified.…”

Characterizing the Interactions between a Naturally Primed Immunoglobulin A and Its Conserved Bacteroides thetaiotaomicron Species-specific Epitope in Gnotobiotic Mice

“…(26 and 27). Cloned IgA-producing lines were identified using procedures detailed in a previous publication (23).…”

“…thetaiotaomicron VPI-5482 contains eight distinct capsular polysaccharide synthesis loci, each composed of 15-32 genes. A panel of eight isogenic mutants, generated with the suicide vector pGERM to block expression of genes in each locus (23), was used to test the CPS epitope specificity of mAb 260.8.…”

“…To explore the species, strain, and epitope level specificities of the IgA response and its effects on the biological properties and fitness of targeted components of the microbiota, we created a simplified, defined gnotobiotic mouse model (23). Bacteroides thetaiotaomicron is a prominent member of the adult human gut microbiota.…”

Generation of colonic IgA-secreting cells in the caecal patch

“…In the intestinal lumen, secretory IgA binds pathogens and pathogen-derived antigens to limit their invasion into the body 5,6 . In addition, secretory IgA contributes to the maintenance of gut homeostasis by regulating the activities and compositions of commensal bacteria 5,[7][8][9] . Dysregulation of gut homeostasis caused by defective IgA responses can compromise host defenses against intestinal pathogenic bacteria and correlates with autoimmune diseases [10][11][12] .…”