Open AccessBinding of the non‐typeable Haemophilus influenzae lipooligosaccharide to the PAF receptor initiates host cell signalling
Author(s) -
Swords W. Edward,
Ketterer Margaret R.,
Shao Jianqiang,
Campbell Colleen A.,
Weiser Jeffrey N.,
Apicella Michael A.
Publication year - 2001
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.1462-5822.2001.00132.x
Subject(s) - biology , microbiology and biotechnology , haemophilus influenzae , platelet activating factor receptor , receptor , pertussis toxin , platelet activating factor , bacterial adhesin , wortmannin , phosphatidylinositol , immunology , signal transduction , g protein , biochemistry , antagonist , virulence , antibiotics , gene
Non‐typeable Haemophilus influenzae (NTHi) invades host cells by binding of the platelet‐activating factor (PAF) receptor via lipooligosaccharide (LOS) glycoforms containing phosphorylcholine (ChoP). The effect of NTHi infection on host cell signalling and its role in NTHi invasion was examined. The infection of human bronchial epithelial cells with NTHi 2019 increased cytosolic Ca 2+ levels, and the invasion of bronchial cells by NTHi 2019 was inhibited by pretreatment with the cell‐permeant intracellular Ca 2+ chelator BAPTA‐AM ( P = 0.022) or thapsigargin ( P = 0.016). Cytosolic inositol phosphate (IP) levels were also increased after infection with NTHi 2019 ( P < 0.001), but not after infection with isogenic mutants expressing altered LOS glycoforms lacking ChoP. PAF receptor antagonist reduced NTHi 2019‐stimulated IP production in a dose‐dependent manner. NTHi 2019 invasion was inhibited by pertussis toxin (PTX) and the phosphatidylinositol‐3‐kinase inhibitors wortmannin and LY294002. The less invasive strain NTHi 7502 also initiated IP production, but was unaffected by PAF receptor antagonist or PTX. These data demonstrate that the binding of the PAF receptor by NTHi initiates receptor coupling to a PTX‐sensitive heterotrimeric G protein complex, resulting in a multifactorial host cell signal cascade and bacterial invasion. Moreover, the data suggest that NTHi strains initiate cell signalling and invade by different mechanisms, and that invasion mediated by PAF receptor activation is more efficient than macropinocytosis.