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Journal of Neuroinflammation

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Open Access 01-12-2012 | Research

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

Authors: Rosalind P Herbert, Julie Harris, Kim Pei Chong, Jamie Chapman, Adrian K West, Meng Inn Chuah

Published in: Journal of Neuroinflammation | Issue 1/2012

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.

Mori I, Goshima F, Imai Y, Kohsaka S, Sugiyama T, Yoshida T, Yokochi T, Nishiyama Y, Kimura Y: Olfactory receptor neurons prevent dissemination of neurovirulent influenza A virus into the brain by undergoing virus-induced apoptosis. J Gen Virol 2002, 83:2109–2116.CrossRefPubMed

Claeys S, de Belder T, Holtappels G, Gevaert P, Verhasselt B, van Cauwenberge P, Bachert C: Human beta-defensins and toll-like receptors in the upper airway. Allergy 2003, 58:748–753.CrossRefPubMed

Charles PC, Walters E, Margolis F, Johnston RE: Mechanism of neuroinvasion of Venezuelan equine encephalitis virus in the mouse. Virology 1995, 208:662–671.CrossRefPubMed

Bi Z, Barna M, Komatsu T, Reiss CS: Vesicular stomatitis virus infection of the central nervous system activates both innate and acquired immunity. J Virol 1995, 69:6466–6472.PubMedPubMedCentral

van Ginkel FW, McGhee JR, Watt JM, Campos-Torres A, Parish LA, Briles DE: Pneumococcal carriage results in ganglioside-mediated olfactory tissue infection. PNAS 2003, 100:14363–14367.CrossRefPubMedPubMedCentral

Harris JA, West AK, Chuah MI: Olfactory ensheathing cells: Nitric oxide production and innate immunity. Glia 2009, 57:1848–1857.CrossRefPubMed

Vincent AJ, Taylor JM, Choi-Lundberg DL, West AK, Chuah MI: Genetic expression profile of olfactory ensheathing cells is distinct from that of Schwann cells and astrocytes. Glia 2005, 51:132–147.CrossRefPubMed

Vincent AJ, West AK, Chuah MI: Glial modulation of the innate immune response: Olfactory ensheathing cells join the melee? In In New Research on Innate Immunity. Edited by: Durand MMCV. Nova Science Publishers, Inc, New York; 2008:339–349.

Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, Kakizaki M, Takagi S, Nomiyama H, Schall TJ, Yoshie O: Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell 1997, 91:521–530.CrossRefPubMed

10.

Ruitenberg MJ, Vukovic J, Blomster L, Hall JM, Jung S, Filgueira L, McMenamin PG, Plant GW: CX3CL1/fractalkine regulates branching and migration of monocyte-derived cells in the mouse olfactory epithelium. J Neuroimmunol 2008, 205:80–85.CrossRefPubMed

11.

Verhaagen J, Oestreicher AB, Grillo M, Khew-Goodall YS, Gispen WH, Margolis FL: Neuroplasticity in the olfactory system: differential effects of central and peripheral lesions of the primary olfactory pathway on the expression of B-50/GAP43 and the olfactory marker protein. J Neurosci Res 1990, 26:31–44.CrossRefPubMed

12.

Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976, 72:248–254.CrossRefPubMed

13.

Hale DM, Ray S, Leung JY, Holloway AF, Chung RS, West AK, Chuah MI: Olfactory ensheathing cells moderate nuclear factor kappaB translocation in astrocytes. Mol Cell Neurosci 2011, 46:213–221.CrossRefPubMed

14.

Montero Domínguez M, González B, Zimmer J: Neuroprotective effects of the anti-inflammatory compound triflusal on ischemia-like neurodegeneration in mouse hippocampal slice cultures occur independent of microglia. Exp Neurol 2009, 218:11–23.CrossRefPubMed

15.

Seifert S, Pannell M, Uckert W, Färber K, Kettenmann H: Transmitter- and hormone-activated Ca2+ responses in adult microglia/brain macrophages in situ recorded after viral transduction of a recombinant Ca2+ sensor. Cell Calcium 2011, 49:365–375.CrossRefPubMed

16.

Leung JY, Chapman JA, Harris JA, Hale D, Chung RS, West AK, Chuah MI: Olfactory ensheathing cells are attracted to, and can endocytose, bacteria. Cell Mol Life Sci 2008, 65:2732–2739.CrossRefPubMed

17.

Cummings DM, Emge DK, Small SL, Margolis FL: Pattern of olfactory bulb innervation returns after recovery from reversible peripheral deafferentation. J Comp Neurol 2000, 421:362–373.CrossRefPubMed

18.

Tennent R, Chuah MI: Ultrastructural study of ensheathing cells in early development of olfactory axons. Dev Brain Res 1996, 95:135–139.CrossRef

19.

Bauer S, Kerr BJ, Patterson PH: The neuropoietic cytokine family in development, plasticity, disease and injury. Nat Rev Neurosci 2007, 8:221–232.CrossRefPubMed

20.

Islam Z, Harkema JR, Pestka JJ: Satratoxin G from the black mold Stachybotrys chartarum evokes olfactory sensory neuron loss and inflammation in the murine nose and brain. Environ Health Perspect 2006, 114:1099–1107.CrossRefPubMedPubMedCentral

21.

Wang JE, Jorgensen PF, Almlof M, Thiemermann C, Foster SJ, Aasen AO, Solberg R: Peptidoglycan and lipoteichoic acid from Staphylococcus aureus induce tumor necrosis factor alpha, interleukin 6 (IL-6), and IL-10 production in both T cells and monocytes in a human whole blood model. Infect Immun 2000, 68:3965–3970.CrossRefPubMedPubMedCentral

22.

Nau GJ, Richmond JF, Schlesinger A, Jennings EG, Lander ES, Young RA: Human macrophage activation programs induced by bacterial pathogens. Proc Natl Acad Sci USA 2002, 99:1503–1508.CrossRefPubMedPubMedCentral

23.

Kielian T, Bearden ED, Baldwin AC, Esen N: IL-1 and TNF-alpha play a pivotal role in the host immune response in a mouse model of Staphylococcus aureus-induced experimental brain abscess. J Neuropathol Exp Neurol 2004, 63:381–396.CrossRefPubMed

24.

Hegg CC, Au E, Roskams AJ, Lucero MT: PACAP is present in the olfactory system and evokes calcium transients in olfactory receptor neurons. J Neurophysiol 2003, 90:2711–2719.CrossRefPubMedPubMedCentral

25.

Kanekar S, Gandham M, Lucero MT: PACAP protects against TNF[alpha]-induced cell death in olfactory epithelium and olfactory placodal cell lines. Mol Cell Neurosci 2010, 45:345–354.CrossRefPubMedPubMedCentral

26.

Nan B, Getchell ML, Partin JV, Getchell TV: Leukemia inhibitory factor, interleukin-6, and their receptors are expressed transiently in the olfactory mucosa after target ablation. J Comp Neurol 2001, 435:60–77.CrossRefPubMed

27.

Yamashita T, Sawamoto K, Suzuki S, Suzuki N, Adachi K, Kawase T, Mihara M, Ohsugi Y, Abe K, Okano H: Blockade of interleukin-6 signaling aggravates ischemic cerebral damage in mice: possible involvement of Stat3 activation in the protection of neurons. J Neurochem 2005, 94:459–468.CrossRefPubMed

28.

Vincent AJ, West AK, Chuah MI: Morphological and functional plasticity of olfactory ensheathing cells. J Neurocytol 2005, 34:65–80.CrossRefPubMed

29.

Vincent AJ, Choi-Lundberg DL, Harris JA, West AK, Chuah MI: Bacteria and PAMPs activate NFκB and Gro production in a subset of olfactory ensheathing cells and astrocytes but not in Schwann cells. Glia 2007, 55:905–916.CrossRefPubMed

30.

Xie QW, Kashiwabara Y, Nathan C: Role of transcription factor NF-kappa B/Rel in induction of nitric oxide synthase. J Biol Chem 1994, 269:4705–4708.PubMed

31.

Liu Z, Hsu H, Goeddel DV, Karin M: Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-[kappa] B activation prevents cell death. Cell 1996, 87:565–576.CrossRefPubMed

32.

Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB: NF-κB activation by tumour necrosis factor requires the Akt serine-threonine kinase. Nature 1999, 401:82–85.CrossRefPubMed

33.

Matsusaka T, Fujikawa K, Nishio Y, Mukaida N, Matsushima K, Kishimoto T, Akira S: Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8. Proc Natl Acad Sci 1993, 90:10193–10197.CrossRefPubMedPubMedCentral

34.

Libermann TA, Baltimore D: Activation of interleukin-6 gene expression through the NF-kappa B transcription factor. Mol Cell Biol 1990, 10:2327–2334.CrossRefPubMedPubMedCentral

35.

Roet KC, Bossers K, Franssen EH, Ruitenberg MJ, Verhaagen J: A meta-analysis of microarray-based gene expression studies of olfactory bulb-derived olfactory ensheathing cells. Exp Neurol 2011, 229:10–45.CrossRefPubMed

36.

Gauldie J, Richards C, Harnish D, Lansdorp P, Baumann H: Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci USA 1987, 84:7251–7255.CrossRefPubMedPubMedCentral

37.

Lotz M, Jirik F, Kabouridis P, Tsoukas C, Hirano T, Kishimoto T, Carson DA: B cell stimulating factor 2/interleukin 6 is a costimulant for human thymocytes and T lymphocytes. J Exp Med 1988, 167:1253–1258.CrossRefPubMed

38.

Macedo-Ramos H, Campos FSO, Carvalho LA, Ramos IB, Teixeira LM, De Souza W, Cavalcante LA, Baetas-da-Cruz W: Olfactory ensheathing cells as putative host cells for Streptococcus pneumoniae: evidence of bacterial invasion via mannose receptor-mediated endocytosis. Neurosci Res 2011, 69:308–313.CrossRefPubMed

39.

Pearce BD, Hobbs MV, McGraw TS, Buchmeier MJ: Cytokine induction during T-cell-mediated clearance of mouse hepatitis virus from neurons in vivo. J Virol 1994, 68:5483–5495.PubMedPubMedCentral

40.

Lalancette-Hébert M, Phaneuf D, Soucy G, Weng YC, Kriz J: Live imaging of Toll-like receptor 2 response in cerebral ischaemia reveals a role of olfactory bulb microglia as modulators of inflammation. Brain 2009, 132:940–954.CrossRefPubMed

41.

Wang ZL, Cheng SM, Ma MM, Ma YP, Yang JP, Xu GL, Liu XF: Intranasally delivered bFGF enhances neurogenesis in adult rats following cerebral ischemia. Neurosci Lett 2008, 446:30–35.CrossRefPubMed

42.

Yang JP, Liu HJ, Cheng SM, Wang ZL, Cheng X, Yu HX, Liu XF: Direct transport of VEGF from the nasal cavity to brain. Neurosci Lett 2009, 449:108–111.CrossRefPubMed

43.

Marks DR, Tucker K, Cavallin MA, Mast TG, Fadool DA: Awake intranasal insulin delivery modifies protein complexes and alters memory, anxiety, and olfactory behaviors. J Neurosci 2009, 29:6734–6751.CrossRefPubMedPubMedCentral

44.

Hanisch U-K: Microglia as a source and target of cytokines. Glia 2002, 40:140–155.CrossRefPubMed

45.

Lalancette-Hébert Ml, Moquin A, Choi AO, Kriz J, Maysinger D: Lipopolysaccharide-QD micelles induce marked induction of TLR2 and lipid droplet accumulation in olfactory bulb microglia. Mol Pharm 2010, 7:1183–1194.CrossRef

Title: Cytokines and olfactory bulb microglia in response to bacterial challenge in the compromised primary olfactory pathway
Authors: Rosalind P Herbert
Julie Harris
Kim Pei Chong
Jamie Chapman
Adrian K West
Meng Inn Chuah
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2012
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/1742-2094-9-109

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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