Olfactory nerves extend from the nasal cavity to the central nervous system and provide therefore, a direct route for pathogenic infection of the brain. Since actual infection by this route remains relatively uncommon, powerful endogenous mechanisms for preventing microbial infection must exist, but these remain poorly understood. Our previous studies unexpectedly revealed that the unique glial cells that ensheath olfactory nerves, olfactory ensheathing cells (OECs), expressed components of the innate immune response. In this study, we show that OECs are able to detect and respond to bacterial challenge via the synthesis of nitric oxide. In vitro studies revealed that inducible nitric oxide synthase (iNOS) mRNA and protein were present in Escherichia coli- and Staphylococcus aureus-incubated OECs, but were barely detectable in untreated OECs. Neuronal NOS and endothelial NOS were not expressed by OECs pre- and post-bacterial incubation. Nuclear translocation of nuclear factor kappa B (NFkB), detectable in the majority of OECs 1 h following bacterial incubation, preceded iNOS induction which resulted in the production of nitric oxide. NG-methyl-L-arginine significantly attenuated nitric oxide (P < 0.001) and nitrite production (P < 0.001) by OECs. In rat olfactory mucosa which was compromised by irrigation with 0.17M zinc sulfate or 0.7% Triton X-100 to facilitate bacterial infiltration, OECs contributed to a robust synthesis of iNOS. These data strongly support the hypothesis that OECs are an essential component of the innate immune response against bacterial invasion of the central nervous system via olfactory nerves.

Item Type:	Refereed Article
Keywords:	innate immune response; nuclear factor kB; olfactory pathway; neuroglia; neuroprotection
Research Division:	Medical and Health Sciences
Research Group:	Immunology
Research Field:	Innate Immunity
Objective Division:	Health
Objective Group:	Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:	Immune System and Allergy
Author:	Harris, JA (Dr Julie Harris)
Author:	West, AK (Professor Adrian West)
Author:	Chuah, MI (Dr Inn Chuah)
ID Code:	59115
Year Published:	2009
Web of Science® Times Cited:	25
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2009-11-18
Last Modified:	2012-03-01
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