Binding of the non-typeable Haemophilus influenzae lipooligosaccharide to the PAF receptor initiates host cell signalling

W Edward Swords; Margaret R Ketterer; Jianqiang Shao; Colleen A Campbell; Jeffrey N Weiser; Michael A Apicella

doi:10.1046/j.1462-5822.2001.00132.x

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Binding of the non-typeable Haemophilus influenzae lipooligosaccharide to the PAF receptor initiates host cell signalling

Journal article

Open access

Peer reviewed

Binding of the non-typeable Haemophilus influenzae lipooligosaccharide to the PAF receptor initiates host cell signalling

W Edward Swords, Margaret R Ketterer, Jianqiang Shao, Colleen A Campbell, Jeffrey N Weiser and Michael A Apicella

Cellular microbiology, Vol.3(8), pp.525-536

08/2001

DOI: 10.1046/j.1462-5822.2001.00132.x

PMID: 11488814

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Abstract

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 Ca2+ levels, and the invasion of bronchial cells by NTHi 2019 was inhibited by pretreatment with the cell-permeant intracellular Ca2+ 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.

Bronchi - microbiology

Cell Line

Inositol Phosphates - biosynthesis

Respiratory Mucosa - cytology

Humans

Receptors, G-Protein-Coupled

Lipopolysaccharides - metabolism

Receptors, Cell Surface

Bacterial Adhesion

Respiratory Mucosa - microbiology

Bacterial Typing Techniques

Platelet Membrane Glycoproteins - metabolism

Bronchi - metabolism

Cytosol - metabolism

Respiratory Mucosa - metabolism

Haemophilus influenzae - pathogenicity

Bronchi - cytology

Calcium Signaling

Haemophilus influenzae - classification

Details

Title: Subtitle: Binding of the non-typeable Haemophilus influenzae lipooligosaccharide to the PAF receptor initiates host cell signalling
Creators: W Edward Swords - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Margaret R Ketterer
Jianqiang Shao
Colleen A Campbell
Jeffrey N Weiser
Michael A Apicella
Resource Type: Journal article
Publication Details: Cellular microbiology, Vol.3(8), pp.525-536
DOI: 10.1046/j.1462-5822.2001.00132.x
PMID: 11488814
ISSN: 1462-5814
eISSN: 1462-5822
Grant note: AI 24616 / NIAID NIH HHS AI 65298 / NIAID NIH HHS AI 38446 / NIAID NIH HHS AI 07511 / NIAID NIH HHS AI 44231 / NIAID NIH HHS
Language: English
Date published: 08/2001
Academic Unit: Microbiology and Immunology; Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984094672402771

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