Cooperation of Gastric Mononuclear Phagocytes with Helicobacter pylori during Colonization

• Published in: The Journal of immunology (1950) 2017-04, Vol.198 (8), p.3195-3204
• Main Authors: Viladomiu, Monica, Bassaganya-Riera, Josep, Tubau-Juni, Nuria, Kronsteiner, Barbara, Leber, Andrew, Philipson, Casandra W, Zoccoli-Rodriguez, Victoria, Hontecillas, Raquel
• Format: Article
• Language: English
• Subjects: Accumulation; Animals; Bacteria; Bisphosphonates; CD11b antigen; Clodronic acid; Colonization; CX3CR1 protein; Disease Models, Animal; Flow Cytometry; Gastric mucosa; Gastric Mucosa - immunology; Gastric Mucosa - microbiology; Helicobacter Infections - immunology; Helicobacter pylori; Immunoregulation; Infections; Inflammation; Interleukin 10; Interleukin 17; Lamina propria; Leukocytes (mononuclear); Liposomes; Lymphocytes T; Macrophages; Macrophages - immunology; Mice; Mice, Inbred C57BL; Microbiota; Myeloid cells; Neutralization; Phagocytes; Rodents; Stomach
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1601902

, 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 F4/80 CD64 CX CR1 macrophages in the gastric lamina propria. Depletion of phagocytic cells by clodronate liposomes in wild-type mice resulted in a reduction of gastric 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 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 F4/80 CD64 CX CR1 mononuclear phagocytes that contribute to maintaining high levels of loads in the stomach by modulating effector T cell responses at the gastric mucosa.