Helicobacter pylori, the dominant member of the human gastric microbiota, elicits immunoregulatory responses implicated in protective versus pathological outcomes. To evaluate the role of macrophages during infection, we employed a system with a shifted proinflammatory macrophage phenotype by deleting PPARγ in myeloid cells and found a 5- to 10-fold decrease in gastric bacterial loads. Higher levels of colonization in wild-type mice were associated with increased presence of mononuclear phagocytes and in particular with the accumulation of CD11b+F4/80hiCD64+CX3CR1+ macrophages in the gastric lamina propria. Depletion of phagocytic cells by clodronate liposomes in wild-type mice resulted in a reduction of gastric H. pylori colonization compared with nontreated mice. PPARγ-deficient and macrophage-depleted mice presented decreased IL-10–mediated myeloid and T cell regulatory responses soon after infection. IL-10 neutralization during H. pylori infection led to increased IL-17–mediated responses and increased neutrophil accumulation at the gastric mucosa. In conclusion, we report the induction of IL-10–driven regulatory responses mediated by CD11b+F4/80hiCD64+CX3CR1+ mononuclear phagocytes that contribute to maintaining high levels of H. pylori loads in the stomach by modulating effector T cell responses at the gastric mucosa.
This work was supported by National Institute of Allergy and Infectious Diseases Contract HHSN272201000056C (to J.B.-R.) and by funds from the Nutritional Immunology and Molecular Medicine Laboratory.
The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
The online version of this article contains supplemental material.
- Received November 10, 2016.
- Accepted February 8, 2017.
- Copyright © 2017 by The American Association of Immunologists, Inc.