Proteobacteria-specific IgA regulates maturation of the intestinal microbiota

Abstract

The intestinal microbiota changes dynamically from birth to adulthood. In this study we identified γ-Proteobacteria as a dominant phylum present in newborn mice that is suppressed in normal adult microbiota. The transition from a neonatal to a mature microbiota was in part regulated by induction of a γ-Proteobacteria-specific IgA response. Neocolonization experiments in germ-free mice further revealed a dominant Proteobacteria-specific IgA response triggered by the immature microbiota. Finally, a role for B cells in the regulation of microbiota maturation was confirmed in IgA-deficient mice. Mice lacking IgA had persistent intestinal colonization with γ-Proteobacteria that resulted in sustained intestinal inflammation and increased susceptibility to neonatal and adult models of intestinal injury. Collectively, these results identify an IgA-dependent mechanism responsible for the maturation of the intestinal microbiota.

Keywords: :

• IgA
• microbiota
• proteobacteria
• colitis
• necrotizing enterocolitis

10.4161/gmic.26489

Disclosure of Potential Conflicts of Interest

No potential conflict of interest was disclosed.

Acknowledgements

We would like to thank Cassie Behrendt and Charmaine Clements for germ-free mouse husbandry. This research was supported by NIH R01 AI08263 and a Burroughs Wellcome Foundation Investigators in the Pathogenesis of Infectious Diseases award to FY, NIH R01 DK070855 and the Howard Hughes Medical Institute to LVH, NIH R01 HL093535, Children’s Medical Center Foundation Grant and the William Buchanan Chair to RCS and NIH K12 1K12HD068369 and Children’s Medical Center Foundation Grant to JM.

Supplemental Materials

Supplemental materials may be found here: www.landesbioscience.com/journals/gutmicrobes/article/26489