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Cytokines and olfactory bulb microglia in response to bacterial challenge in the compromised primary olfactory pathway

Citation

Herbert, RP and Harris, J and Chong, KP and Chapman, J and West, AK and Chuah, MI, Cytokines and olfactory bulb microglia in response to bacterial challenge in the compromised primary olfactory pathway, Journal of Neuroinflammation, 9, (109) Article 109. ISSN 1742-2094 (2012) [Refereed Article]


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Licensed under Creative Commons Attribution 2.0 Generic (CC BY 2.0) http://creativecommons.org/licenses/by/2.0/

DOI: doi:10.1186/1742-2094-9-109

Abstract

Background: The primary olfactory pathway is a potential route through which microorganisms from the periphery could potentially access the central nervous system. Our previous studies demonstrated that if the olfactory epithelium was damaged, bacteria administered into the nasal cavity induced nitric oxide production in olfactory ensheathing cells. This study investigates the cytokine profile of olfactory tissues as a consequence of bacterial challenge and establishes whether or not the bacteria are able to reach the olfactory bulb in the central nervous system.

Methods: The olfactory epithelium of C57BL/6 mice was damaged by unilateral Triton X-100 nasal washing, and Staphylococcus aureus was administered ipsilaterally 4 days later. Olfactory mucosa and bulb were harvested 6 h, 24 h and 5 days after inoculation and their cytokine profile compared to control tissues. The fate of S. aureus and the response of bulbar microglia were examined using fluorescence microscopy and transmission electron microscopy.

Results: In the olfactory mucosa, administered S. aureus was present in supporting cells of the olfactory epithelium, and macrophages and olfactory nerve bundles in the lamina propria. Fluorescein isothiocyanate-conjugated S. aureus was observed within the olfactory mucosa and bulb 6 h after inoculation, but remained restricted to the peripheral layers up to 5 days later. At the 24-h time point, the level of interleukin-6 (IL-6) and tumour necrosis factor-α in the compromised olfactory tissues challenged with bacteria (12,466  956 pg/ml and 552  193 pg/ml, respectively) was significantly higher than that in compromised olfactory tissues alone (6,092  1,403 pg/ml and 80  2 pg/ml, respectively). Immunohistochemistry confirmed that IL-6 was present in several cell types including olfactory ensheathing cells and mitral cells of the olfactory bulb. Concurrently, there was a 4.4-, 4.5- and 2.8-fold increase in the density of iNOS-expressing cells in the olfactory mucosa, olfactory nerve and glomerular layers combined, and granule layer of the olfactory bulb, respectively.

Conclusions: Bacteria are able to penetrate the immunological defence of the compromised olfactory mucosa and infiltrate the olfactory bulb within 6 h even though a proinflammatory profile is mounted. Activated microglia may have a role in restricting bacteria to the outer layers of the olfactory bulb.

Item Details

Item Type:Refereed Article
Keywords:olfactory mucosa, innate immunity, cytokines, bacterial infection, microglia, olfactory ensheathing cells
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Herbert, RP (Ms Rosalind Herbert)
Author:Harris, J (Dr Julie Harris)
Author:Chong, KP (Ms Kim Chong)
Author:Chapman, J (Dr Jamie Chapman)
Author:West, AK (Professor Adrian West)
Author:Chuah, MI (Dr Inn Chuah)
ID Code:79302
Year Published:2012
Web of Science® Times Cited:20
Deposited By:Menzies Institute for Medical Research
Deposited On:2012-08-29
Last Modified:2016-09-30
Downloads:258 View Download Statistics

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