title: Intestinal inflammation responds to microbial tissue load independent of pathogen/non-pathogen discrimination.
abstract: The intestinal immune system mounts inflammatory responses to pathogens but tolerates harmless commensal microbiota. Various mechanisms for pathogen/non-pathogen discrimination have been proposed but their general relevance for inflammation control is unclear. Here, we compared intestinal responses to pathogenic Salmonella and non-pathogenic E. coli. Both microbes entered intestinal Peyer's patches and, surprisingly, induced qualitatively and quantitatively similar initial inflammatory responses revealing a striking discrimination failure. Diverging inflammatory responses only occurred when Salmonella subsequently proliferated and induced escalating neutrophil infiltration, while harmless E. coli was rapidly cleared from the tissue and inflammation resolved. Transient intestinal inflammation induced by harmless E. coli tolerized against subsequent exposure thereby preventing chronic inflammation during repeated exposure. These data revealed a striking failure of the intestinal immune system to discriminate pathogens from harmless microbes based on distinct molecular signatures. Instead, appropriate intestinal responses to gut microbiota might be ensured by immediate inflammatory responses to any rise in microbial tissue loads, and desensitization after bacterial clearance.
authors.affiliation: Junior Group Mucosal Infections, Hannover Medical School, Hannover, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Willer
authors.forename: Beatrice
authors.initials: B
authors.lastname: Müller
authors.forename: Dirk
authors.initials: D
authors.lastname: Bumann
mesh_terms: D000818:Animals; D004926:Escherichia coli / Q000472:pathogenicity; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000276:immunology; D010581:Peyer's Patches / Q000276:immunology / Q000382:microbiology; D019779:Salmonella enterica / Q000472:pathogenicity*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4