Helicobacter bilis infection accelerates and H. hepaticus infection delays the development of colitis in multiple drug resistance-deficient (mdr1a-/-) mice.
mdr1a-deficient mice lack P-glycoprotein and spontaneously develop colitis with age. Helicobacter spp. are gram-negative organisms that have been associated with colitis in certain mouse strains, but Helicobacter spp. have been excluded as contributing to the spontaneous colitis that develops in mdr1a-/- mice. We wished to determine whether infection with either H. bilis or H. hepaticus would accelerate the development of inflammatory bowel disease (IBD) in mdr1a-/- mice. We found that H. bilis infection induced diarrhea, weight loss, and IBD in mdr1a-/- mice within 6 to 17 weeks post-inoculation and before the expected onset of spontaneous IBD. Histopathology of H. bilis-induced IBD included crypt hyperplasia, inflammatory cell infiltrates, crypt abscesses, and obliteration of normal gut architecture. Reverse transcription-polymerase chain reaction and Taqman analysis from colonic tissue showed increased transcripts for interferon-gamma and interleukin-10 from H. bilis-infected colitic mdr1a-/- mice. Additionally, mesenteric lymph nodes had increased cellularity with expansion of CD4+ and CD8+ T cells and B cells and increased proliferation to soluble H. bilis antigens with elaboration of interferon-gamma, tumor necrosis factor-alpha and interleukin-10. In contrast, H. hepaticus infection of mdr1a-/- mice did not accelerate disease but rather delayed the onset of spontaneous colitis which was milder in severity. mdr1a-/- mice infected with Helicobacter spp. may provide a useful tool to explore the pathogenesis of microbial-induced IBD in a model with a presumed epithelial cell "barrier" defect.
Maggio-Price
Lillian
L
Department of Comparative Medicine, School of Medicine, University of Washington, Box 357190, Seattle, WA 981295, USA.
Shows
Donna
D
Waggie
Kim
K
Burich
Andrew
A
Zeng
Weiping
W
Escobar
Sabine
S
Morrissey
Phil
P
Viney
Joanne L
JL
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics* / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D003092:Colitis / Q000209:etiology / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018432:Drug Resistance, Multiple; D005260:Female; D016998:Helicobacter / Q000502:physiology*; D016481:Helicobacter Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D007136:Immunoglobulins / Q000097:blood; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D007422:Intestines / Q000473:pathology / Q000502:physiology; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic
D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D016207:Cytokines; D007136:Immunoglobulins; C095122:multidrug resistance protein 3