Open AccessRole of phosphatidylinositol 3‐kinase in the binding of Bordetella pertussis to human monocytes
Author(s) -
Ishibashi Yoshio,
Yoshimura Katsuaki,
Nishikawa Akemi,
Claus Sarah,
Laudanna Carlo,
Relman David A.
Publication year - 2002
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1046/j.1462-5822.2002.00235.x
Subject(s) - bordetella pertussis , wortmannin , integrin , biology , ly294002 , tyrosine phosphorylation , phosphatidylinositol , integrin alpha m , phosphorylation , filamentous haemagglutinin adhesin , pertactin , integrin, beta 6 , pertussis toxin , microbiology and biotechnology , signal transduction , receptor , g protein , biochemistry , flow cytometry , bacteria , genetics
Summary Bordetella pertussis , the causative agent of whooping cough, adheres to human monocytes by means of filamentous haemagglutinin (FHA), a bacterial surface protein that is recognized by complement receptor type 3 (CR3, α M β 2 integrin). Previous work has shown that an FHA Arg‐Gly‐Asp (RGD, residues 1097–1099) site interacts with a complex composed of leucocyte response integrin (LRI, α v β 3 integrin) and integrin‐associated protein (IAP, CD47) on human monocytes, resulting in enhancement of CR3‐mediated bacterial binding. However, the pathway that mediates α v β 3 ‐α M β 2 integrin signalling remains to be characterized. Here we describe the involvement of phosphatidylinositol 3‐kinase (PI3‐K) in this pathway. Wortmannin and LY294002, inhibitors of PI3‐K, reduced α v β 3 /IAP‐upregulated, CR3‐associated bacterial binding to human monocytes. B. pertussis infection of human monocytes resulted in a marked recruitment of cellular PI3‐K to the sites of B. pertussis contact. In contrast, cells infected with an isogenic strain carrying a G1098A mutation at the FHA RGD site did not show any recruitment of PI3‐K. We found that ligation of FHA by α v β 3 /IAP induced RGD‐dependent tyrosine phosphorylation of a 60 kDa protein, which associated with IAP and PI3‐K in human monocytes. These results suggest that PI3‐K and a tyrosine phosphorylated 60 kDa protein may be involved in this biologically important integrin signalling pathway.