title: Genetic background of IL-10(-/-) mice alters host-pathogen interactions with Campylobacter jejuni and influences disease phenotype.
abstract: We hypothesized that particular genetic backgrounds enhance rates of colonization, increase severity of enteritis, and allow for extraintestinal spread when inbred IL-10(-/-) mice are infected with pathogenic C. jejuni. Campylobacter jejuni stably colonized C57BL/6 and NOD mice, while congenic strains lacking IL-10 developed typhlocolitis following colonization that mimicked human campylobacteriosis. However, IL-10 deficiency alone was not necessary for the presence of C. jejuni in extraintestinal sites. C3H/HeJ tlr4(-/-) mice that specifically express the Cdcs1 allele showed colonization and limited extraintestinal spread without enteritis implicating this interval in the clinical presentation of C. jejuni infection. Furthermore, when the IL-10 gene is inactivated as in C3Bir tlr4(-/-) IL-10(-/-) mice, enteritis and intensive extraintestinal spread were observed, suggesting that clinical presentations of C. jejuni infection are controlled by a complex interplay of factors. These data demonstrate that lack of IL-10 had a greater effect on C. jejuni induced colitis than other immune elements such as TLR4 (C3H/HeJ, C3Bir IL-10(-/-)), MHC H-2g7, diabetogenic genes, and CTLA-4 (NOD) and that host genetic background is in part responsible for disease phenotype. C3Bir IL-10(-/-) mice where Cdcs1 impairs gut barrier function provide a new murine model of C. jejuni and can serve as surrogates for immunocompromised patients with extraintestinal spread.
authors.affiliation: Comparative Enteric Diseases Laboratory, Michigan State University, East Lansing, MI 48824, USA. mansfie4@cvm.msu.edu
authors.forename: L S
authors.initials: LS
authors.lastname: Mansfield
authors.forename: J S
authors.initials: JS
authors.lastname: Patterson
authors.forename: B R
authors.initials: BR
authors.lastname: Fierro
authors.forename: A J
authors.initials: AJ
authors.lastname: Murphy
authors.forename: V A
authors.initials: VA
authors.lastname: Rathinam
authors.forename: J J
authors.initials: JJ
authors.lastname: Kopper
authors.forename: N I
authors.initials: NI
authors.lastname: Barbu
authors.forename: T J
authors.initials: TJ
authors.lastname: Onifade
authors.forename: J A
authors.initials: JA
authors.lastname: Bell
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D002169:Campylobacter Infections / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016123:Campylobacter jejuni / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D004751:Enteritis / Q000235:genetics / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D054884:Host-Pathogen Interactions; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010641:Phenotype
chemical_list: D000907:Antibodies, Bacterial; D016753:Interleukin-10