SLAM controls killing of bacteria through regulation of phosphatidylinositol-3-phosphate in phagosomes (133.31)

Abstract

Abstract Macrophages eradicate pathogens by phagosomal reactive oxygen species, nitric oxide and by exposure to phagolysosomal enzymes. Whereas a number of surface receptors are requisite for recognition and entry of bacteria into the phagosome, their role in bacterial killing is largely unknown. Here we show that the surface receptor SLAM (Slamf1, Cd150) enters the macrophage phagosome together with Gram-negative, but not with Gram-positive bacteria. In the bacterial phagosome, SLAM regulates production of phosphatidylinositol-3-phosphate (PI3P), which is a key factor in the assembly of the active NADPH-oxidase (Nox2) enzyme complex, as well as in phagosome maturation. Consequently, these two bactericidal processes are defective in the absence of SLAM, resulting in an impaired clearance of attenuated S. typhimurium sseB- in SLAM-deficient mice. This is the first example of a surface receptor, which is a co-stimulatory molecule in T cell responses, also governing distinct functions in intracellular vesicles of phagocytic cells. This work was supported by a grant from the NIH (AI-15066)