Genetic background of IL-10(-/-) mice alters host-pathogen interactions with Campylobacter jejuni and influences disease phenotype.
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.
Mansfield
L S
LS
Comparative Enteric Diseases Laboratory, Michigan State University, East Lansing, MI 48824, USA. mansfie4@cvm.msu.edu
Patterson
J S
JS
Fierro
B R
BR
Murphy
A J
AJ
Rathinam
V A
VA
Kopper
J J
JJ
Barbu
N I
NI
Onifade
T J
TJ
Bell
J A
JA
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
D000907:Antibodies, Bacterial; D016753:Interleukin-10