title: Inflammation-associated alterations to the intestinal microbiota reduce colonization resistance against non-typhoidal Salmonella during concurrent malaria parasite infection.
abstract: Childhood malaria is a risk factor for disseminated infections with non-typhoidal Salmonella (NTS) in sub-Saharan Africa. While hemolytic anemia and an altered cytokine environment have been implicated in increased susceptibility to NTS, it is not known whether malaria affects resistance to intestinal colonization with NTS. To address this question, we utilized a murine model of co-infection. Infection of mice with Plasmodium yoelii elicited infiltration of inflammatory macrophages and T cells into the intestinal mucosa and increased expression of inflammatory cytokines. These mucosal responses were also observed in germ-free mice, showing that they are independent of the resident microbiota. Remarkably, P. yoelii infection reduced colonization resistance of mice against S. enterica serotype Typhimurium. Further, 16S rRNA sequence analysis of the intestinal microbiota revealed marked changes in the community structure. Shifts in the microbiota increased susceptibility to intestinal colonization by S. Typhimurium, as demonstrated by microbiota reconstitution of germ-free mice. These results show that P. yoelii infection, via alterations to the microbial community in the intestine, decreases resistance to intestinal colonization with NTS. Further they raise the possibility that decreased colonization resistance may synergize with effects of malaria on systemic immunity to increase susceptibility to disseminated NTS infections.
authors.affiliation: Department of Medical Microbiology &Immunology, University of California at Davis, One Shields Avenue, Davis CA 95616.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Mooney
authors.affiliation: Department of Medical Microbiology &Immunology, University of California at Davis, One Shields Avenue, Davis CA 95616.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Lokken
authors.affiliation: Department of Medical Microbiology &Immunology, University of California at Davis, One Shields Avenue, Davis CA 95616.
authors.forename: Mariana X
authors.initials: MX
authors.lastname: Byndloss
authors.affiliation: Department of Medical Microbiology &Immunology, University of California at Davis, One Shields Avenue, Davis CA 95616.
authors.forename: Michael D
authors.initials: MD
authors.lastname: George
authors.affiliation: Department of Medical Microbiology &Immunology, University of California at Davis, One Shields Avenue, Davis CA 95616.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Velazquez
authors.affiliation: Department of Medical Microbiology &Immunology, University of California at Davis, One Shields Avenue, Davis CA 95616.
authors.forename: Franziska
authors.initials: F
authors.lastname: Faber
authors.affiliation: Department of Medical Microbiology &Immunology, University of California at Davis, One Shields Avenue, Davis CA 95616.|School of Veterinary Medicine, St. George's University, Grenada, West Indies.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Butler
authors.affiliation: Department of Medical Microbiology &Immunology, University of California at Davis, One Shields Avenue, Davis CA 95616.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Walker
authors.affiliation: Department of Microbiology, The Ohio State University, Columbus, OH 43210 USA.|Center for Microbial Interface Biology, The Ohio State University, Columbus, OH 43210 USA.|Department of Medical Microbiology and Immunology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Ali
authors.affiliation: Department of Medical Microbiology &Immunology, University of California at Davis, One Shields Avenue, Davis CA 95616.
authors.forename: Rashaun
authors.initials: R
authors.lastname: Potts
authors.affiliation: Department of Medical Microbiology &Immunology, University of California at Davis, One Shields Avenue, Davis CA 95616.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Tiffany
authors.affiliation: Department of Microbiology, The Ohio State University, Columbus, OH 43210 USA.|Center for Microbial Interface Biology, The Ohio State University, Columbus, OH 43210 USA.|Department of Microbial Infection and Immunity, The Ohio State University, 460 W. 12th Ave, Columbus, OH 43210.
authors.forename: Brian M M
authors.initials: BM
authors.lastname: Ahmer
authors.affiliation: Department of Medical Microbiology &Immunology, University of California at Davis, One Shields Avenue, Davis CA 95616.
authors.forename: Shirley
authors.initials: S
authors.lastname: Luckhart
authors.affiliation: Department of Medical Microbiology &Immunology, University of California at Davis, One Shields Avenue, Davis CA 95616.
authors.forename: Renée M
authors.initials: RM
authors.lastname: Tsolis
mesh_terms: D000818:Animals; D002432:Cecum / Q000276:immunology / Q000382:microbiology / Q000469:parasitology; D060085:Coinfection / Q000276:immunology / Q000382:microbiology / Q000469:parasitology; D004198:Disease Susceptibility; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology / Q000469:parasitology; D008288:Malaria / Q000276:immunology / Q000382:microbiology*; D008810:Mice, Inbred C57BL; D010967:Plasmodium yoelii / Q000502:physiology*; D012480:Salmonella Infections / Q000276:immunology / Q000382:microbiology* / Q000469:parasitology; D012486:Salmonella typhimurium / Q000502:physiology*