Role for Complement in Development of
Helicobacter
-Induced Gastritis in Interleukin-10-Deficient Mice
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Published:2003-12
Issue:12
Volume:71
Page:7140-7148
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ISSN:0019-9567
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Container-title:Infection and Immunity
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language:en
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Short-container-title:Infect Immun
Author:
Ismail Hanan F.1, Zhang Juan1, Lynch Richard G.2, Wang Yi3, Berg Daniel J.1
Affiliation:
1. Department of Internal Medicine 2. Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa 52242 3. Alexion Pharmaceuticals, Inc., Cheshire, Connecticut 06410
Abstract
ABSTRACT
The mechanisms by which the immune response can eradicate gastric
Helicobacter
infection are unknown. We hypothesized that
Helicobacter
-induced activation of the complement system could promote both inflammation and eradication of
Helicobacter
from the stomach. In vitro studies demonstrated that
Helicobacter felis
activates complement in normal mouse serum but not in serum from Rag2
−/−
mice, indicating that
H. felis
activates complement through the classical pathway. Next, we infected complement-depleted wild-type control and interleukin-10-deficient (IL-10
−/−
) mice with
H. felis. Helicobacter
infection of wild-type mice elicited a mild, focal gastritis and did not alter serum complement levels. Infection of IL-10
−/−
mice with
H. felis
elicited severe gastritis. After the initial colonization, the IL-10
−/−
mice completely cleared
Helicobacter
from the stomach by day 8. In contrast to wild-type mice,
H. felis
-infected IL-10
−/−
mice had a marked increase in serum complement levels. Complement depletion of wild-type mice did not affect the intensity of gastric inflammation or the extent of
Helicobacter
colonization compared to that for the wild-type control mice. In contrast, complement depletion of
Helicobacter
-infected IL-10
−/−
mice decreased the severity of gastritis, decreased the
Helicobacter
-induced infiltration of neutrophils into the stomach, and delayed the clearance of bacteria. In vitro studies of stimulated splenocytes and neutrophils from IL-10
−/−
mice produced a twofold increase in complement production compared to that for wild-type mice. Pretreatment with IL-10 inhibited this increase. These studies identify a role for complement in the local immune response to gastric
Helicobacter
in IL-10
−/−
mice and suggest a role for IL-10 in the regulation of complement production.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
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