Characterization of the Chanzyme TRPM7 in Macrophages

The innate immune system forms the foundation of immunity through pathogen recognition and maintenance of tissue homeostasis. In particular, myeloid phagocytes are specialized in recognizing host- and microbe-derived molecules to direct cytokine production, phagocytosis, and antigen presentation. The receptors for immunomodulatory molecules require signals from secondary messengers, such as Ca2+ ions, to modulate signal transduction and drive pro- and anti-inflammatory cellular programs. Electrical signals have long been associated with core functions of innate immunity, and recent discoveries have begun to define the ion channels associated with inflammatory signal transduction and phagocytosis. In this dissertation, I describe the role of ion channels in innate immunity. TRP-family ion channels are essential cellular sensors that transduce sensory inputs into electrical signals, predominantly though calcium signals, to control cellular function. In particular, my research focuses on characterization of TRPM7 in macrophages. We discovered that TRPM7 is required for activation of macrophages by LPS and regulates macrophage phagocytosis of apoptotic cells.