Enhanced M1 macrophage polarization in human helicobacter pylori-associated atrophic gastritis and in vaccinated mice.
BACKGROUND
Infection with Helicobacter pylori triggers a chronic gastric inflammation that can progress to atrophy and gastric adenocarcinoma. Polarization of macrophages is a characteristic of both cancer and infection, and may promote progression or resolution of disease. However, the role of macrophages and their polarization during H. pylori infection has not been well defined.


RESULTS
By using a mouse model of infection and gastric biopsies from 29 individuals, we have analyzed macrophage recruitment and polarization during H. pylori infection by flow cytometry and real-time PCR. We found a sequential recruitment of neutrophils, eosinophils and macrophages to the gastric mucosa of infected mice. Gene expression analysis of stomach tissue and sorted macrophages revealed that gastric macrophages were polarized to M1 after H. pylori infection, and this process was substantially accelerated by prior vaccination. Human H. pylori infection was characterized by a mixed M1/M2 polarization of macrophages. However, in H. pylori-associated atrophic gastritis, the expression of inducible nitric oxide synthase was markedly increased compared to uncomplicated gastritis, indicative of an enhanced M1 macrophage polarization in this pre-malignant lesion.


CONCLUSIONS
These results show that vaccination of mice against H. pylori amplifies M1 polarization of gastric macrophages, and that a similar enhanced M1 polarization is present in human H. pylori-induced atrophic gastritis.
Department of Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
Marianne
M
Quiding-Järbrink
Sukanya
S
Raghavan
Malin
M
Sundquist
D000818:Animals; D051940:B7-2 Antigen / Q000276:immunology / Q000378:metabolism; D016764:Cell Polarity / Q000276:immunology*; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D005757:Gastritis, Atrophic / Q000276:immunology* / Q000382:microbiology; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014611:Vaccination
D051940:B7-2 Antigen; C111792:CCL18 protein, human; D019742:Chemokines, CC; D052247:Nitric Oxide Synthase Type II