Editors' ChoiceImmunology

SLAMming Bacteria

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Science Signaling  05 Oct 2010:
Vol. 3, Issue 142, pp. ec304
DOI: 10.1126/scisignal.3142ec304

SLAMF (signaling lymphocyte activation molecule family) receptors have established roles as adhesion and costimulatory molecules in various immune cells, and Berger et al. uncovered an additional role for SLAMF receptors in recognizing, phagocytosing, and killing bacteria. Slamf1–/– mice did not clear the gram-negative bacterium Escherichia coli, but they were indistinguishable from wild-type mice in clearing the gram-positive bacteria Staphylococcus aureus. The NADPH oxidase 2 (NOX2) enzyme complex produces reactive oxygen species (ROS) to kill bacteria, and, in response to E. coli but not to S. aureus, macrophages from Slamf1–/– mice produced lower amounts of ROS as well as bacteria-containing phagosomes that acidified more rapidly. Phagosomes containing E. coli, but not those containing S. aureus, took longer to mature in Slamf1–/– macrophages than in wild-type macrophages; in addition, cargo delivery to phagosomes in Slamf1–/– macrophages was delayed. SLAM was detected in phagosomes containing E. coli, but not S. aureus. The N-terminal ectodomain of SLAM recognized the outer membrane porins OmpC and OmpF, and greater amounts of ROS were produced in response to purified OmpC in wild-type compared with Slamf1–/– macrophages. Phosphatidylinositol 3-phosphate [PtdIns(3)P] stimulates NOX activity and promotes phagosomal maturation. Accordingly, production of PtdIns(3)P was lower in E. coli–containing phagosomes in Slamf1–/– macrophages, and transfection of SLAM into RAW264.7 macrophages increased PtdIns(3)P content in phagosomes. Through beclin-1 and the adaptor protein EAT-2, SLAM interacted with Vps34, the kinase that generates PtdIns(3)P, and Vps15, the regulatory subunit of Vps34. Thus, besides acting as adhesion and costimulatory molecules, SLAMF proteins also serve as sensors for specific membrane proteins in gram-negative bacteria and promote the clearance of these bacteria.

S. B. Berger, X. Romero, C. Ma, G. Wang, W. A. Faubion, G. Liao, E. Compeer, M. Keszei, L. Rameh, N. Wang, M. Boes, J. R. Regueiro, H.-C. Reinecker, C. Terhorst, SLAM is a microbial sensor that regulates bacterial phagosome functions in macrophages. Nat. Immunol. 11, 920–927 (2010). [PubMed]

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