title: Disease tolerance mediated by microbiome E. coli involves inflammasome and IGF-1 signaling.
abstract: Infections and inflammation can lead to cachexia and wasting of skeletal muscle and fat tissue by as yet poorly understood mechanisms. We observed that gut colonization of mice by a strain of Escherichia coli prevents wasting triggered by infections or physical damage to the intestine. During intestinal infection with the pathogen Salmonella Typhimurium or pneumonic infection with Burkholderia thailandensis, the presence of this E. coli did not alter changes in host metabolism, caloric uptake, or inflammation but instead sustained signaling of the insulin-like growth factor 1/phosphatidylinositol 3-kinase/AKT pathway in skeletal muscle, which is required for prevention of muscle wasting. This effect was dependent on engagement of the NLRC4 inflammasome. Therefore, this commensal promotes tolerance to diverse diseases.
authors.affiliation: Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Alexandria M Palaferri
authors.initials: AM
authors.lastname: Schieber
authors.affiliation: Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Yujung Michelle
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Integrative Genomics and Bioinformatics Core, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Max W
authors.initials: MW
authors.lastname: Chang
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Mathias
authors.initials: M
authors.lastname: Leblanc
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Brett
authors.initials: B
authors.lastname: Collins
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Downes
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Evans
authors.affiliation: Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. jayres@salk.edu.
authors.forename: Janelle S
authors.initials: JS
authors.lastname: Ayres
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053898:Biosynthetic Pathways; D019117:Burkholderia; D019121:Burkholderia Infections / Q000150:complications; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology*; D058847:Inflammasomes / Q000276:immunology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007422:Intestines / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D018482:Muscle, Skeletal / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012480:Salmonella Infections / Q000150:complications; D012486:Salmonella typhimurium; D019282:Wasting Syndrome / Q000209:etiology / Q000276:immunology* / Q000382:microbiology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D058847:Inflammasomes; C512299:Ipaf protein, mouse; D007334:Insulin-Like Growth Factor I; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt