SLAM is a microbial sensor that regulates bacterial

phagosome functions in macrophages

Cox Terhorst, et al. 2010. Nature Immunology. 11(10), 920-927

Speaker: Sheng- huei Lin Chung (林張聖彙)               Time: 14:00~15:00, Jan.5, 2011

Commentator: Lien- I Hor (何漣漪老師)                    Place: Room 601

Abstract

        Phagocytosis has essential functions in immunity. Phagocytes, such as macrophage, neutrophils and dendritic cells, are able to internalize and destruct microorganisms following recognition by pathogen receptor, which subsequently promote antigen presentation and the development of adaptive immunity. Here the authors discovered  signaling lymphocytic activation molecule (SLAM),  a transmembrane protein on most hematopoietic cell surface, can function not only as a costimulatory molecule but also as a microbial sensor that recognizes gram-negative bacteria and regulates phagosome development in macrophage. SLAM controls NOX2 activity and phagosomal maturation, which are two pivotal bactericidal processes in phagocyte after entering the gram negative-containing phagosome, following interaction with bacterial outer membrane proteins OmpCand OmpF. In the phagosome, SLAM recruites a complex containing the intracellular class III phosphatidylinositol kinase Vps34, its regulatory protein kinase Vps15 and the autophagy-associated molecule beclin-1 to the phagosomal membrane. The Vps34 was identified as a main kinase to convert phosphatidylinositol into PtdIns, an important molecule which interacts with both PX domain of the NOX2 subunit p40phox and the FYVE domain of the tethering molecule EEA1, a requisite step for successful phagosomal and endosomal maturation. Take together, SLAM acts as a vital regulator in the innate immune defense against OmpC and OmpF containing-gram­negative bacteria in macrophages by independently regulating two main bactericidal processes: phagosome maturation and the production of free radical species by the NOX2 complex.

References:

1.      Ronald S. Flannagan, et al. Antimicrobial mechanisms of phagocytes and bacterial evasion strategies. Nature Review Microbiology. 2009；7: 355-366

2.      Cox Terhorst, et al. SLAM family receptors and the SLAM-associated protein

(SAP) modulate T cell functions. Journal of Biological Chemistry. 2008；283:2108–2119