Affiliation:
1. Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
Abstract
ABSTRACT
Helicobacter cinaedi
colonizes a wide host range, including rodents, and may be an emerging zoonotic agent. Colonization parameters, pathology, serology, and inflammatory responses to wild-type
H. cinaedi
(WT
Hc
) were evaluated in B6.129P2-
IL-10
tm1Cgn
(IL-10
−/−
) mice for 36 weeks postinfection (WPI) and in C57BL/6 (B6) mice for 12 WPI. Because cytolethal distending toxin (CDT) may be a virulence factor, IL-10
−/−
mice were also infected with the
cdtB
Hc
and
cdtB
-N
Hc
isogenic mutants and evaluated for 12 WPI. Consistent with other murine enterohepatic helicobacters, WT
Hc
did not cause typhlocolitis in B6 mice, but mild to severe lesions developed at the cecocolic junction in IL-10
−/−
mice, despite similar colonization levels of WT
Hc
in the cecum and colon of both B6 and IL-10
−/−
mice. WT
Hc
and
cdtB
mutants also colonized IL-10
−/−
mice to a similar extent, but infection with either
cdtB
mutant resulted in attenuated typhlocolitis and hyperplasia compared to infection with WT
Hc
(
P
< 0.03), and only WT
Hc
infection caused dysplasia and intramucosal carcinoma. WT
Hc
and
cdtB
Hc
mutant infection of IL-10
−/−
mice elevated mRNA expression of tumor necrosis factor alpha, inducible nitric oxide synthase, and gamma interferon in the cecum, as well as elevated Th1-associated serum immunoglobulin G2a
b
compared to infection of B6 mice (
P
< 0.05). Although no hepatitis was noted, liver samples were PCR positive at various time points for WT
Hc
or the
cdtB
Hc
mutant in approximately 33% of IL-10
−/−
mice and in 10 to 20% of WT
Hc
-infected B6 mice. These results indicate that WT
Hc
can be used to model inflammatory bowel disease in IL-10
−/−
mice and that CDT contributes to the virulence of
H. cinaedi
.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
58 articles.
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