Distinct mechanisms of internalization of Neisseria gonorrhoeae by members of the CEACAM receptor family involving Rac1- and Cdc42-dependent and -independent pathways

被引:67
作者
Billker, O
Popp, A
Brinkmann, V
Wenig, G
Schneider, J
Caron, E
Meyer, TF
机构
[1] Max Planck Inst Infekt Biol, Mol Biol Abt, D-10117 Berlin, Germany
[2] Univ Freiburg, Inst Immunbiol, D-79104 Freiburg, Germany
[3] UCL, MRC, Mol Cell Biol Lab, London WC1E 6BT, England
关键词
carcinoembryonic antigen-related cellular; adhesion molecules; Cdc42; invasion; phagocytosis; Rac1;
D O I
10.1093/emboj/21.4.560
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Opa adhesins of pathogenic Neisseria species target four members of the human carcinoembryonic anti. gen-related cellular adhesion molecule (CEACAM) family. CEACAM receptors mediate opsonization-independent phagocytosis of Neisseria gonorrhoeae by human granulocytes and each receptor individually can mediate gonococcal invasion of epithelial cells. We show here that gonococcal internalization occurs by distinct mechanisms depending on the CEACAM receptor expressed. For the invasion of epithelial cell lines via CEACAM1 and CEACAM6, a pathogen-directed reorganization of the actin cytoskeleton is not required. In marked contrast, ligation of CEACAM3 triggers a dramatic but localized reorganization of the host cell surface leading to highly efficient engulfment of bacteria in a process regulated by the small GTPases Rac1 and Cdc42, but not Rho. Two tyrosine residues of a cytoplasmic immune receptor tyrosine-based activating motif of CEACAM3 are essential for the induction of phagocytic actin structures and subsequent gonococcal internalization. The granulocyte-specific CEACAM3 receptor has properties of a single chain phagocytic receptor and may thus contribute to innate immunity by the elimination of Neisseria and other CEACAM-binding pathogens that colonize human mucosal surfaces.
引用
收藏
页码:560 / 571
页数:12
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