Depletion of Neutrophils in IL-10−/− Mice Delays Clearance of Gastric Helicobacter Infection and Decreases the Th1 Immune Response to Helicobacter

Abstract

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.