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Cooperation of Gastric Mononuclear Phagocytes with Helicobacter pylori during Colonization.


ABSTRACT: 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 PPAR? 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. PPAR?-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.

SUBMITTER: Viladomiu M 

PROVIDER: S-EPMC5380565 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Cooperation of Gastric Mononuclear Phagocytes with <i>Helicobacter pylori</i> during Colonization.

Viladomiu Monica M   Bassaganya-Riera Josep J   Tubau-Juni Nuria N   Kronsteiner Barbara B   Leber Andrew A   Philipson Casandra W CW   Zoccoli-Rodriguez Victoria V   Hontecillas Raquel R  

Journal of immunology (Baltimore, Md. : 1950) 20170306 8


<i>Helicobacter pylori</i>, 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 p  ...[more]

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