TRPM2 Ion Channels Regulate Macrophage Polarization and Gastric Inflammation During Helicobacter pylori Infection


Calcium signaling in phagocytes is essential for cellular activation, migration, and the potential resolution of infection or inflammation. The generation of reactive oxygen species (ROS) via activation of NADPH (nicotinamide adenine dinucleotide phosphate)-oxidase activity in macrophages has been linked to altered intracellular calcium concentrations. Because of its role as an oxidative stress sensor in phagocytes, we investigated the function of the cation channel transient receptor potential melastatin 2 (TRPM2) in macrophages during oxidative stress responses induced by Helicobacter pylori infection. We show that Trpm2-/- mice, when chronically infected with H. pylori, exhibit increased gastric inflammation and decreased bacterial colonization compared with wild-type (WT) mice. The absence of TRPM2 triggers greater macrophage production of inflammatory mediators and promotes classically activated macrophage M1 polarization in response to H. pylori. TRPM2-deficient macrophages upon H. pylori stimulation are unable to control intracellular calcium levels, which results in calcium overloading. Furthermore, increased intracellular calcium in TRPM2-/- macrophages enhanced mitogen-activated protein kinase and NADPH-oxidase activities, compared with WT macrophages. Our data suggest that augmented production of ROS and inflammatory cytokines with TRPM2 deletion regulates oxidative stress in macrophages and consequently decreases H. pylori gastric colonization while increasing inflammation in the gastric mucosa.

DOI: 10.1038/mi.2016.60

Cite this paper

@inproceedings{Beceiro2016TRPM2IC, title={TRPM2 Ion Channels Regulate Macrophage Polarization and Gastric Inflammation During Helicobacter pylori Infection}, author={Susana Beceiro and Jana N. Radin and Rupesh Chatuvedi and M Blanca Piazuelo and Dennis J. Horvarth and Hanna H Cortado and Yuanzheng Gu and Beverly R. E. A. Dixon and Chen Gu and Ingo Lange and Dana-Lynn T. Koomoa and Keith T. Wilson and Holly M. Scott Algood and Santiago Partida-Sanchez}, booktitle={Mucosal immunology}, year={2016} }