Human Airway Epithelial Cell Responses to Neisseria lactamica and Purified Porin via Toll-Like Receptor 2-Dependent Signaling

The human airway epithelium is constantly exposed to microbial products from colonizing organisms. Regulation of Toll-like receptor (TLR) expression and specific interactions with bacterial ligands is thought to mitigate exacerbation of inflammatory processes induced by the commensal flora in these...

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Bibliographic Details
Published in:Infection and Immunity 2010-12, Vol.78 (12), p.5314-5323
Main Authors: Liu, Xiuping, Wetzler, Lee M, Oliveira Nascimento, Laura, Massari, Paola
Format: Article
Language:English
Subjects:
Bacteriology
Biological and medical sciences
Cell Line
Enzyme-Linked Immunosorbent Assay
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation, Bacterial - physiology
Host Response and Inflammation
Humans
Immunity, Cellular - immunology
Immunity, Cellular - physiology
Interleukin-8 - immunology
Interleukin-8 - physiology
Microbiology
Miscellaneous
Neisseria lactamica
Neisseria lactamica - immunology
Neisseria meningitidis
Neisseriaceae Infections - immunology
Porins - immunology
Porins - physiology
Respiratory Mucosa - immunology
Respiratory Mucosa - microbiology
Signal Transduction - immunology
Signal Transduction - physiology
Toll-Like Receptor 1 - immunology
Toll-Like Receptor 1 - physiology
Toll-Like Receptor 2 - immunology
Toll-Like Receptor 2 - physiology
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Summary:The human airway epithelium is constantly exposed to microbial products from colonizing organisms. Regulation of Toll-like receptor (TLR) expression and specific interactions with bacterial ligands is thought to mitigate exacerbation of inflammatory processes induced by the commensal flora in these cells. The genus Neisseria comprises pathogenic and commensal organisms that colonize the human nasopharynx. Neisseria lactamica is not associated with disease, but N. meningitidis occasionally invades the host, causing meningococcal disease and septicemia. Upon colonization of the airway epithelium, specific host cell receptors interact with numerous Neisseria components, including the PorB porin, at the immediate bacterial-host cell interface. This major outer membrane protein is expressed by all Neisseria strains, regardless of pathogenicity, but its amino acid sequence varies among strains, particularly in the surface-exposed regions. The interaction of Neisseria PorB with TLR2 is essential for driving TLR2/TLR1-dependent cellular responses and is thought to occur via the porin's surface-exposed loop regions. Our studies show that N. lactamica PorB is a TLR2 ligand but its binding specificity for TLR2 is different from that of meningococcal PorB. Furthermore, N. lactamica PorB is a poor inducer of proinflammatory mediators and of TLR2 expression in human airway epithelial cells. These effects are reproduced by whole N. lactamica organisms. Since the responsiveness of human airway epithelial cells to colonizing bacteria is in part regulated via TLR2 expression and signaling, commensal organisms such as N. lactamica would benefit from expressing a product that induces low TLR2-dependent local inflammation, likely delaying or avoiding clearance by the host.
ISSN:0019-9567
1098-5522
DOI:10.1128/IAI.00681-10