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J Immunol. 2015 Apr 1;194(7):3259-66. doi: 10.4049/jimmunol.1401260. Epub 2015 Feb 20.

Myeloid HIF-1 is protective in Helicobacter pylori-mediated gastritis.

Author information

1
INSERM, U1016, Institut Cochin, 75014 Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, 75014 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France;
2
Department of Pediatrics, University of California San Diego, La Jolla, CA 92093;
3
INSERM, U1016, Institut Cochin, 75014 Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, 75014 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France; Centre de Génétique et de Physiologie Moléculaire et Cellulaire, Unité Mixte de Recherche Centre National de la Recherche Scientifique 5534, Université Claude Bernard Lyon 1, Lyon, 69622 Villeurbanne Cedex, France;
4
Hôpital Cochin, 75014 Paris, France;
5
Equipe d'Accueil 4340, Université de Versailles, and Hôpital Ambroise Paré, Assistance Publique des Hôpitaux de Paris, 92104 Boulogne, France; and.
6
Institut Pasteur, 75015 Paris, France.
7
INSERM, U1016, Institut Cochin, 75014 Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, 75014 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France; carole.peyssonnaux@inserm.fr.

Abstract

Helicobacter pylori infection triggers chronic inflammation of the gastric mucosa that may progress to gastric cancer. The hypoxia-inducible factors (HIFs) are the central mediators of cellular adaptation to low oxygen levels (hypoxia), but they have emerged recently as major transcriptional regulators of immunity and inflammation. No studies have investigated whether H. pylori affects HIF signaling in immune cells and a potential role for HIF in H. pylori-mediated gastritis. HIF-1 and HIF-2 expression was examined in human H. pylori-positive gastritis biopsies. Subsequent experiments were performed in naive and polarized bone marrow-derived macrophages from wild-type (WT) and myeloid HIF-1α-null mice (HIF-1(Δmyel)). WT and HIF-1(Δmyel) mice were inoculated with H. pylori by oral gavage and sacrificed 6 mo postinfection. HIF-1 was specifically expressed in macrophages of human H. pylori-positive gastritis biopsies. Macrophage HIF-1 strongly contributed to the induction of proinflammatory genes (IL-6, IL-1β) and inducible NO synthase in response to H. pylori. HIF-2 expression and markers of M2 macrophage differentiation were decreased in response to H. pylori. HIF-1(Δmyel) mice inoculated with H. pylori for 6 mo presented with a similar bacterial colonization than WT mice but, surprisingly, a global increase of inflammation, leading to a worsening of the gastritis, measured by an increased epithelial cell proliferation. In conclusion, myeloid HIF-1 is protective in H. pylori-mediated gastritis, pointing to the complex counterbalancing roles of innate immune and inflammatory phenotypes in driving this pathology.

PMID:
25710915
DOI:
10.4049/jimmunol.1401260
[Indexed for MEDLINE]
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