Role of Inflammatory Monocytes in Vaccine-Induced Reduction of Helicobacter felis Infection.
Despite the proven ability of immunization to reduce Helicobacter infection in mouse models, the precise mechanism of protection has remained elusive. In this study, we evaluated the role of inflammatory monocytes in the vaccine-induced reduction of Helicobacter felis infection. We first showed by using flow cytometric analysis that Ly6C(low) major histocompatibility complex class II-positive chemokine receptor type 2 (CCR2)-positive CD64(+) inflammatory monocytes accumulate in the stomach mucosa during the vaccine-induced reduction of H. felis infection. To determine whether inflammatory monocytes played a role in the protection, these cells were depleted with anti-CCR2 depleting antibodies. Indeed, depletion of inflammatory monocytes was associated with an impaired vaccine-induced reduction of H. felis infection on day 5 postinfection. To determine whether inflammatory monocytes had a direct or indirect role, we studied their antimicrobial activities. We observed that inflammatory monocytes produced tumor necrosis factor alpha and inducible nitric oxide synthase (iNOS), two major antimicrobial factors. Lastly, by using a Helicobacter in vitro killing assay, we showed that mouse inflammatory monocytes and activated human monocytes killed H. pylori in an iNOS-dependent manner. Collectively, these data show that inflammatory monocytes play a direct role in the immunization-induced reduction of H. felis infection from the gastric mucosa.
Service of Gastroenterology and Hepatology, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
Mati
M
Moyat
Universitätsklinikum Regensburg Innere Medizin II-Nephrologie, Regensburg, Germany.
Matthias
M
Mack
UNISciences, University of Lausanne, UniLabs, Lausanne, Switzerland.
Hanifa
H
Bouzourene
Service of Gastroenterology and Hepatology, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland dominique.velin@chuv.ch.
Dominique
D
Velin
D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005260:Female; D016481:Helicobacter Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D044922:Helicobacter felis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
D001428:Bacterial Vaccines; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II