Rhythmicity of intestinal IgA responses confers oscillatory commensal microbiota mutualism.

Abstract

Interactions between the mammalian host and commensal microbiota are enforced through a range of immune responses that confer metabolic benefits and promote tissue health and homeostasis. Immunoglobulin A (IgA) responses directly determine the composition of commensal species that colonize the intestinal tract but require significant metabolic resources to fuel antibody production by tissue-resident plasma cells. Here we demonstrate IgA responses are subject to diurnal regulation over the course of a circadian day. Specifically, the magnitude of IgA secretion, as well as the transcriptome of tissue-resident IgA+ plasma cells, were found to exhibit rhythmicity. Oscillatory IgA responses were found to be entrained by time of feeding, and in-part coordinated by the plasma cell-intrinsic circadian clock. Moreover, reciprocal interactions between the host and microbiota dictated oscillatory dynamics amongst the commensal microbial community and its associated transcriptional and metabolic activity, in an IgA-dependent manner. Together our findings suggest circadian networks comprising intestinal IgA, the diet and the microbiota converge to align circadian biology in the intestinal tract and to ensure host-microbial mutualism.