Depletion of neutrophils in IL-10(-/-) mice delays clearance of gastric Helicobacter infection and decreases the Th1 immune response to Helicobacter.
Gastric infection with Helicobacter induces a lymphocyte-rich mucosal inflammation that contains a minor population of neutrophilic granulocytes. The function of neutrophils in the local immune response to gastric Helicobacter infection remains unknown. To investigate this issue, we conducted experiments in neutrophil-depleted control wild-type (wt) and IL-10(-/-) mice infected with Helicobacter felis by gastric lavage. Infection of wt mice elicited a mild, focal gastritis and a Helicobacter-specific Th1 immune response. In wt mice Helicobacter colonization of the stomach was persistent and progressively increased during the 29 days of observation. Infection of IL-10(-/-) mice with H. felis elicited a severe chronic gastritis and a greatly enhanced Helicobacter-specific Th1 immune response, as compared with wt mice. After initial colonization, the IL-0(-/-) mice completely cleared Helicobacter from the stomach by day 8. The gastric inflammation in wt and IL-10(-/-) mice contained modest numbers of neutrophils. The intensity of gastric inflammation and the extent of Helicobacter colonization were similar in control and in neutrophil-depleted wt mice. In contrast, neutrophil depletion of Helicobacter-infected IL-10(-/-) mice decreased the severity of gastritis, modulated the Helicobacter-specific Th1 immune response, and delayed the clearance of bacteria from the stomach. These studies identify a role for neutrophils in the local and systemic immune response to gastric Helicobacter in IL-10(-/-) mice.
Ismail
Hanan F
HF
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
Fick
Pamela
P
Zhang
Juan
J
Lynch
Richard G
RG
Berg
Daniel J
DJ
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005756:Gastritis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D016998:Helicobacter / Q000254:growth & development / Q000276:immunology*; D016481:Helicobacter Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics; D007964:Leukocytosis / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D008212:Lymphocyte Depletion; D051379:Mice; D018345:Mice, Knockout; D009503:Neutropenia / Q000235:genetics / Q000276:immunology*; D009504:Neutrophils / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000382:microbiology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*
D000942:Antigens, Bacterial; D016753:Interleukin-10