Murine norovirus: an intercurrent variable in a mouse model of bacteria-induced inflammatory bowel disease.
Murine norovirus (MNV) has recently been recognized as a widely prevalent viral pathogen in mouse colonies and causes disease and mortality in mice with impaired innate immunity. We tested the hypothesis that MNV infection would alter disease course and immune responses in mice with inflammatory bowel disease (IBD). FVB.129P2-Abcb1a(tm1Bor) N7 (Mdr1a-/-) mice develop spontaneous IBD that is accelerated by infection with Helicobacter bilis. As compared with controls, Mdr1a-/- mice coinfected with MNV4 and H. bilis showed greater weight loss and IBD scores indicative of severe colitis, demonstrating that MNV4 can modulate the progression of IBD. Compared with controls, mice inoculated with MNV4 alone had altered levels of serum biomarkers, and flow cytometric analysis of immune cells from MNV4-infected mice showed changes in both dendritic cell (CD11c+) and other nonT cell (CD4- CD8-) populations. Dendritic cells isolated from MNV4-infected mice induced higher IFNgamma production by polyclonal T cells in vitro at 2 d after infection but not at later time points, indicating that MNV4 infection enhances antigen presentation by dendritic cells early after acute infection. These findings indicate that acute infection with MNV4 is immunomodulatory and alters disease progression in a mouse model of IBD.
Lencioni
Karen Chase
KC
Unit for Laboratory Animal Resources, California Institute of Technology, Pasadena, California, USA. kchase@caltech.edu
Seamons
Audrey
A
Treuting
Piper M
PM
Maggio-Price
Lillian
L
Brabb
Thea
T
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000172:deficiency / Q000235:genetics; D000818:Animals; D017250:Caliciviridae Infections / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D016998:Helicobacter / Q000472:pathogenicity; D016481:Helicobacter Infections / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D007108:Immune Tolerance; D007113:Immunity, Innate; D015212:Inflammatory Bowel Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D029322:Norovirus / Q000472:pathogenicity*
D018435:ATP Binding Cassette Transporter, Subfamily B; D007371:Interferon-gamma; C095122:multidrug resistance protein 3