title: Cooperation of Gastric Mononuclear Phagocytes withHelicobacter pyloriduring 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 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 gastricH. pyloricolonization 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 duringH. pyloriinfection 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 ofH. pyloriloads in the stomach by modulating effector T cell responses at the gastric mucosa.
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA 24061.
authors.forename: Monica
authors.initials: M
authors.lastname: Viladomiu
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA 24061.
authors.forename: Josep
authors.initials: J
authors.lastname: Bassaganya-Riera
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA 24061.
authors.forename: Nuria
authors.identifier: 0000-0002-5787-8055
authors.initials: N
authors.lastname: Tubau-Juni
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA 24061.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kronsteiner
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA 24061.
authors.forename: Andrew
authors.initials: A
authors.lastname: Leber
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA 24061.
authors.forename: Casandra W
authors.initials: CW
authors.lastname: Philipson
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA 24061.
authors.forename: Victoria
authors.initials: V
authors.lastname: Zoccoli-Rodriguez
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA 24061 rmagarzo@vt.edu.
authors.forename: Raquel
authors.identifier: 0000-0003-2942-6294
authors.initials: R
authors.lastname: Hontecillas
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000276:immunology* / Q000382:microbiology*; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL