Comparative analysis of the interaction of Helicobacter pylori with human dendritic cells, macrophages, and monocytes |
| |
Authors: | Fehlings Michael Drobbe Lea Moos Verena Renner Viveros Pablo Hagen Jana Beigier-Bompadre Macarena Pang Ervinna Belogolova Elena Churin Yuri Schneider Thomas Meyer Thomas F Aebischer Toni Ignatius Ralf |
| |
Affiliation: | aInstitute of Tropical Medicine and International Health, Charité-Universitätsmedizin Berlin, Berlin, Germany;bDepartment of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany;cMedical Clinic I, Charité-Universitätsmedizin Berlin, Berlin, Germany;dRobert Koch Institute, Berlin, Germany |
| |
Abstract: | Helicobacter pylori may cause chronic gastritis, gastric cancer, or lymphoma. Myeloid antigen-presenting cells (APCs) are most likely involved in the induction and expression of the underlying inflammatory responses. To study the interaction of human APC subsets with H. pylori, we infected monocytes, monocyte-derived dendritic cells (DCs), and monocyte-derived (classically activated; M1) macrophages with H. pylori and analyzed phenotypic alterations, cytokine secretion, phagocytosis, and immunostimulation. Since we detected CD163(+) (alternatively activated; M2) macrophages in gastric biopsy specimens from H. pylori-positive patients, we also included monocyte-derived M2 macrophages in the study. Upon H. pylori infection, monocytes secreted interleukin-1β (IL-1β), IL-6, IL-10, and IL-12p40 (partially secreted as IL-23) but not IL-12p70. Infected DCs became activated, as shown by the enhanced expression of CD25, CD80, CD83, PDL-1, and CCR7, and secreted IL-1β, IL-6, IL-10, IL-12p40, IL-12p70, and IL-23. However, infection led to significantly downregulated CD209 and suppressed the constitutive secretion of macrophage migration inhibitory factor (MIF). H. pylori-infected M1 macrophages upregulated CD14 and CD32, downregulated CD11b and HLA-DR, and secreted mainly IL-1β, IL-6, IL-10, IL-12p40, and IL-23. Activation of DCs and M1 macrophages correlated with increased capacity to induce T-cell proliferation and decreased phagocytosis of dextran. M2 macrophages upregulated CD14 and CD206 and secreted IL-10 but produced less of the proinflammatory cytokines than M1 macrophages. Thus, H. pylori affects the functions of human APC subsets differently, which may influence the course and the outcome of H. pylori infection. The suppression of MIF in DCs constitutes a novel immune evasion mechanism exploited by H. pylori. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|