SLAM is a microbial sensor that regulates bacterial phagosome functions in macrophages

Scott B. Berger, Xavier Romero, Chunyan Ma, Guoxing Wang, William A. Faubion, Gongxian Liao, Ewoud Compeer, Marton Keszei, Lucia Rameh, Ninghai Wang, Marianne Boes, Jose R. Regueiro, Hans Christian Reinecker, Cox Terhorst

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

Phagocytosis is a pivotal process by which macrophages eliminate microorganisms after recognition by pathogen sensors. Here we unexpectedly found that the self ligand and cell surface receptor SLAM functioned not only as a costimulatory molecule but also as a microbial sensor that controlled the killing of Gram-negative bacteria by macrophages. SLAM regulated activity of the NADPH oxidase NOX2 complex and phagolysosomal maturation after entering the phagosome, following interaction with the bacterial outer membrane proteins OmpC and OmpF. SLAM recruited a complex containing the intracellular class III phosphatidylinositol kinase Vps34, its regulatory protein kinase Vps15 and the autophagy-associated molecule beclin-1 to the phagosome, which was responsible for inducing the accumulation of phosphatidylinositol-3-phosphate, a regulator of both NOX2 function and phagosomal or endosomal fusion. Thus, SLAM connects the Gram-negative bacterial phagosome to ubiquitous cellular machinery responsible for the control of bacterial killing.

Original languageEnglish (US)
Pages (from-to)920-927
Number of pages8
JournalNature immunology
Volume11
Issue number10
DOIs
StatePublished - Oct 1 2010
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Berger, S. B., Romero, X., Ma, C., Wang, G., Faubion, W. A., Liao, G., Compeer, E., Keszei, M., Rameh, L., Wang, N., Boes, M., Regueiro, J. R., Reinecker, H. C., & Terhorst, C. (2010). SLAM is a microbial sensor that regulates bacterial phagosome functions in macrophages. Nature immunology, 11(10), 920-927. https://doi.org/10.1038/ni.1931