title: The mucosal inflammatory response to non-typhoidal Salmonella in the intestine is blunted by IL-10 during concurrent malaria parasite infection.
abstract: Coinfection can markedly alter the response to a pathogen, thereby changing its clinical presentation. For example, non-typhoidal Salmonella (NTS) serotypes are associated with gastroenteritis in immunocompetent individuals. In contrast, individuals with severe pediatric malaria can develop bacteremic infections with NTS, during which symptoms of gastroenteritis are commonly absent. Here we report that, in both a ligated ileal loop model and a mouse colitis model, malaria parasites caused a global suppression of gut inflammatory responses and blunted the neutrophil influx that is characteristic of NTS infection. Further, malaria parasite infection led to increased recovery of Salmonella enterica serotype Typhimurium from the draining mesenteric lymph node (MLN) of mice. In the mouse colitis model, blunted intestinal inflammation during NTS infection was independent of anemia but instead required parasite-induced synthesis of interleukin (IL)-10. Blocking of IL-10 in coinfected mice reduced dissemination of S. Typhimurium to the MLN, suggesting that induction of IL-10 contributes to development of disseminated infection. Thus IL-10 produced during the immune response to malaria in this model contributes to suppression of mucosal inflammatory responses to invasive NTS, which may contribute to differences in the clinical presentation of NTS infection in the setting of malaria.
authors.affiliation: School of Medicine, University of California at Davis, Davis, California, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Mooney
authors.affiliation: 1] School of Medicine, University of California at Davis, Davis, California, USA [2] School of Veterinary Medicine, St. George's University, Grenada, West Indies.
authors.forename: B P
authors.initials: BP
authors.lastname: Butler
authors.affiliation: School of Medicine, University of California at Davis, Davis, California, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Lokken
authors.affiliation: 1] School of Medicine, University of California at Davis, Davis, California, USA [2] Escola de Veterinária da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: M N
authors.initials: MN
authors.lastname: Xavier
authors.affiliation: School of Medicine, University of California at Davis, Davis, California, USA.
authors.forename: J Y
authors.initials: JY
authors.lastname: Chau
authors.affiliation: School of Medicine, University of California at Davis, Davis, California, USA.
authors.forename: N
authors.initials: N
authors.lastname: Schaltenberg
authors.affiliation: School of Medicine, University of California at Davis, Davis, California, USA.
authors.forename: S
authors.initials: S
authors.lastname: Dandekar
authors.affiliation: School of Medicine, University of California at Davis, Davis, California, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: George
authors.affiliation: Escola de Veterinária da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: R L
authors.initials: RL
authors.lastname: Santos
authors.affiliation: School of Medicine, University of California at Davis, Davis, California, USA.
authors.forename: S
authors.initials: S
authors.lastname: Luckhart
authors.affiliation: School of Medicine, University of California at Davis, Davis, California, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Tsolis
mesh_terms: D000818:Animals; D005260:Female; D018928:Immunity, Mucosal; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008253:Macaca mulatta; D008288:Malaria / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008643:Mesentery / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D012480:Salmonella Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D012486:Salmonella typhimurium / Q000276:immunology*
chemical_list: C556062:IL10 protein, mouse; D016753:Interleukin-10