title: Enteric Helminths Promote Salmonella Coinfection by Altering the Intestinal Metabolome.
abstract: Intestinal helminth infections occur predominantly in regions where exposure to enteric bacterial pathogens is also common. Helminth infections inhibit host immunity against microbial pathogens, which has largely been attributed to the induction of regulatory or type 2 (Th2) immune responses. Here we demonstrate an additional 3-way interaction in which helminth infection alters the metabolic environment of the host intestine to enhance bacterial pathogenicity. We show that an ongoing helminth infection increased colonization by Salmonella independently of T regulatory or Th2 cells. Instead, helminth infection altered the metabolic profile of the intestine, which directly enhanced bacterial expression of Salmonella pathogenicity island 1 (SPI-1) genes and increased intracellular invasion. These data reveal a novel mechanism by which a helminth-modified metabolome promotes susceptibility to bacterial coinfection.
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver.|Department of Biochemistry and Microbiology, University of Victoria, British Columbia.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Reynolds
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Redpath
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver.
authors.forename: Sophie
authors.initials: S
authors.lastname: Yurist-Doutsch
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver.
authors.forename: Navkiran
authors.initials: N
authors.lastname: Gill
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver.|Department of Microbiology and Immunology, University of British Columbia, Vancouver.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Brown
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver.|Department of Microbiology and Immunology, University of British Columbia, Vancouver.
authors.forename: Joris
authors.initials: J
authors.lastname: van der Heijden
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver.
authors.forename: Tara P
authors.initials: TP
authors.lastname: Brosschot
authors.affiliation: University of Victoria-Genome British Columbia Proteomics Centre.
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver.|Department of Microbiology and Immunology, University of British Columbia, Vancouver.
authors.forename: Natalie C
authors.initials: NC
authors.lastname: Marshall
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver.|Department of Microbiology and Immunology, University of British Columbia, Vancouver.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Woodward
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver.
authors.forename: Yanet
authors.initials: Y
authors.lastname: Valdez
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria, British Columbia.|University of Victoria-Genome British Columbia Proteomics Centre.|Gerald Bronfman Department of Oncology and.|Proteomics Centre, Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Borchers
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver.|Institute of Infection, Immunity and Inflammation, University of Glasgow, United Kingdom ; and.
authors.forename: Georgia
authors.initials: G
authors.lastname: Perona-Wright
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver.|Department of Microbiology and Immunology, University of British Columbia, Vancouver.|Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada.
authors.forename: B Brett
authors.initials: BB
authors.lastname: Finlay
mesh_terms: D000818:Animals; D060085:Coinfection / Q000276:immunology* / Q000382:microbiology / Q000469:parasitology; D006367:HeLa Cells; D006373:Helminthiasis / Q000276:immunology*; D006801:Humans; D007411:Intestinal Diseases, Parasitic / Q000276:immunology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000382:microbiology / Q000469:parasitology; D055442:Metabolome; D051379:Mice; D008810:Mice, Inbred C57BL; D012480:Salmonella Infections / Q000276:immunology*; D012486:Salmonella typhimurium / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology*
keywords: bacterial infection; co-infection; helminths; immunomodulation; intestinal metabolites.