Intraluminal containment of commensal outgrowth in the gut during infection-induced dysbiosis

Cell Host Microbe. 2013 Sep 11;14(3):318-28. doi: 10.1016/j.chom.2013.08.003.

Abstract

Shifts in commensal microbiota composition are emerging as a hallmark of gastrointestinal inflammation. In particular, outgrowth of γ-proteobacteria has been linked to the etiology of inflammatory bowel disease and the pathologic consequences of infections. Here we show that following acute Toxoplasma gondii gastrointestinal infection of mice, control of commensal outgrowth is a highly coordinated process involving both the host response and microbial signals. Notably, neutrophil emigration to the intestinal lumen results in the generation of organized intraluminal structures that encapsulate commensals and limit their contact with the epithelium. Formation of these luminal casts depends on the high-affinity N-formyl peptide receptor, Fpr1. Consequently, after infection, mice deficient in Fpr1 display increased microbial translocation, poor commensal containment, and increased mortality. Altogether, our study describes a mechanism by which the host rapidly contains commensal pathobiont outgrowth during infection. Further, these results reveal Fpr1 as a major mediator of host commensal interaction during dysbiosis.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Bacterial Load
  • Bacterial Translocation / immunology
  • Disease Models, Animal
  • Dysbiosis*
  • Gastrointestinal Tract / immunology
  • Gastrointestinal Tract / microbiology*
  • Gastrointestinal Tract / parasitology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophils / immunology*
  • Proteobacteria / growth & development
  • Proteobacteria / immunology*
  • Receptors, Formyl Peptide / deficiency
  • Receptors, Formyl Peptide / metabolism*
  • Survival Analysis
  • Toxoplasma / growth & development*
  • Toxoplasmosis, Animal / parasitology

Substances

  • Fpr1 protein, mouse
  • Receptors, Formyl Peptide