title: Intraluminal containment of commensal outgrowth in the gut during infection-induced dysbiosis.
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.
authors.affiliation: Program in Barrier Immunity and Repair, Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Molloy
authors.forename: John R
authors.initials: JR
authors.lastname: Grainger
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bouladoux
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Hand
authors.forename: Lily Y
authors.initials: LY
authors.lastname: Koo
authors.forename: Shruti
authors.initials: S
authors.lastname: Naik
authors.forename: Mariam
authors.initials: M
authors.lastname: Quinones
authors.forename: Amiran K
authors.initials: AK
authors.lastname: Dzutsev
authors.forename: Ji-Liang
authors.initials: JL
authors.lastname: Gao
authors.forename: Giorgio
authors.initials: G
authors.lastname: Trinchieri
authors.forename: Philip M
authors.initials: PM
authors.lastname: Murphy
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
mesh_terms: D000818:Animals; D058491:Bacterial Load; D018988:Bacterial Translocation / Q000276:immunology; D004195:Disease Models, Animal; D064806:Dysbiosis; D041981:Gastrointestinal Tract / Q000276:immunology / Q000382:microbiology* / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D020560:Proteobacteria / Q000254:growth & development / Q000276:immunology*; D044042:Receptors, Formyl Peptide / Q000172:deficiency / Q000378:metabolism*; D016019:Survival Analysis; D014122:Toxoplasma / Q000254:growth & development*; D014124:Toxoplasmosis, Animal / Q000469:parasitology
chemical_list: C469988:Fpr1 protein, mouse; D044042:Receptors, Formyl Peptide
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