title: Infection with murine norovirus 4 does not alter Helicobacter-induced inflammatory bowel disease in Il10(-/-) mice.
abstract: Infection of laboratory mice with murine noroviruses (MNV) is widely prevalent. MNV alters various mouse models of disease, including the Helicobacter bilis-induced mouse model of inflammatory bowel disease (IBD) in Mdr1a(--) mice. To further characterize the effect of MNV on IBD, we used mice deficient in the immunoregulatory cytokine IL10 (Il10(-/-) mice). In vitro infection of Il10(-/-) bone marrow-derived macrophages (BMDM) with MNV4 cocultured with H. bilis antigens increased the gene expression of the proinflammatory cytokines IL1β, IL6, and TNFα as compared with that of BMDM cultured with H. bilis antigens only. Therefore, to test the hypothesis that MNV4 infection increases inflammation and alters disease phenotype in H. bilis-infected Il10(-/-) mice, we compared the amount and extent of inflammation in Il10(-/-) mice coinfected with H. bilis and MNV4 with those of mice singly infected with H. bilis. IBD scores, incidence of IBD, or frequency of severe IBD did not differ between mice coinfected with H. bilis and MNV4 and those singly infected with H. bilis. Mice infected with MNV4 only had no appreciable IBD, comparable to uninfected mice. Our findings suggest that, unlike in Mdr1a(-/-) mice, the presence of MNV4 in Il10(-/-) mouse colonies is unlikely to affect the IBD phenotype in a Helicobacter-induced model. However, because MNV4 altered cytokine expression in vitro, our results highlight the importance of determining the potential influence of MNV on mouse models of inflammatory disease, given that MNV has a tropism for macrophages and dendritic cells and that infection is widely prevalent.
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, Washington, USA. chuckhsu@uw.edu.
authors.forename: Charlie C
authors.initials: CC
authors.lastname: Hsu
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Jisun
authors.initials: J
authors.lastname: Paik
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Piper M
authors.initials: PM
authors.lastname: Treuting
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Audrey
authors.initials: A
authors.lastname: Seamons
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Stacey M
authors.initials: SM
authors.lastname: Meeker
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Thea L
authors.initials: TL
authors.lastname: Brabb
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Lillian
authors.initials: L
authors.lastname: Maggio-Price
mesh_terms: D000367:Age Factors; D000818:Animals; D017250:Caliciviridae Infections / Q000235:genetics / Q000276:immunology / Q000821:virology*; D002478:Cells, Cultured; D060085:Coinfection; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005759:Gastroenteritis / Q000235:genetics / Q000276:immunology / Q000821:virology*; D005838:Genotype; D016998:Helicobacter / Q000472:pathogenicity*; D016481:Helicobacter Infections / Q000235:genetics / Q000276:immunology / Q000821:virology*; D054884:Host-Pathogen Interactions; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology / Q000821:virology*; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000821:virology; D018345:Mice, Knockout; D029322:Norovirus / Q000472:pathogenicity*; D010641:Phenotype; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000276:immunology / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C556062:IL10 protein, mouse; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D016753:Interleukin-10