Event

Abstract: Helicobacter pylori (H. pylori) is a gram-positive bacteria present in the gastric mucosa of more than 50% of human population. H. pylori infection induces a combination of effector and regulatory responses in gastric mucosa; however, its lifelong colonization suggests that regulatory responses are predominant. We identified a subset of CD11b+ F4/80hi CD64+ CX3CR1+ macrophages the accumulates in the gastric mucosa starting at 2 weeks post infection. This macrophage response correlates with increased bacterial loads.

To study the role of mononuclear phagocytes, we employed a system of pro-inflammatory shifted macrophages through the deletion of Pparg, an anti-inflammatory transcription factor, in myeloid cells (LysMCre mice). LysMCre mice showed a significant drop in gastric colonization and the identified subset of macrophages was absent. Chemical depletion of macrophages resulted in a decrease in bacterial burden and increased neutrophil infiltration in gastric mucosa.

To track the origin of the macrophages, CCR2 knock out mice were infected and no differences were reported in colonization and phagocytes accumulation in the mucosa compared to WT mice. Further, H. pylori infection induced an IL-10-mediated regulatory response in WT mice. To confirm the role of the anti-inflammatory cytokine, we neutralized IL-10 in vivo and reported a significant decrease of bacterial loads as well as neutrophil accumulation. H. pylori infection induces a myeloid regulatory response mediated by IL-10 that generates an anti-inflammatory environment in gastric mucosa and facilities high levels of colonization.

References:

  1. Kronsteiner B, Bassaganya-Riera J, Philipson C, et al. Systems-wide analyses of mucosal immune responses to Helicobacter pylori at the interface between pathogenicity and symbiosis. Gut Microbes. 2016;7(1):3-21.
  2. Viladomiu M, Bassaganya-Riera J, Tubau-Juni N, et al. Cooperation of Gastric Mononuclear Phagocytes with Helicobacter pylori during Colonization. J Immunol. 2017;198(8):3195-3204.
  3. Varol C, Mildner A, Jung S. Macrophages: development and tissue specialization. Annu Rev Immunol. 2015;33:643-675.
Event Contact:
Dennie Munson   Phone:(540) 231-3053