Bacteria and PAMPs activate nuclear factor kappaB and Gro production in a subset of olfactory ensheathing cells and astrocytes but not in Schwann cells.
The primary olfactory nerves provide uninterrupted conduits for neurotropic pathogens to access the brain from the nasal cavity, yet infection via this route is uncommon. It is conceivable that olfactory ensheathing cells (OECs), which envelope the olfactory nerves along their entire length, provide a degree of immunological protection against such infections. We hypothesized that cultured OECs would be able to mount a biologically significant response to bacteria and pathogen-associated molecular patterns (PAMPs). The response of OECs to Escherichia coli (E. coli) and various PAMPs was compared to that of Schwann cells (SCs), astrocytes (ACs), and microglia (MG). A subset of OECs displayed nuclear localization of nuclear factor kappaB), an inflammatory transcription factor, after treatment with E. coli (20% +/- 5%), lipopolysacchride (33% +/- 9%), and Poly I:C (25% +/- 5%), but not with peptidoglycan or CpG oligonucleotides. ACs displayed a similar level of activation to these treatments, and in addition responded to peptidoglycan. The activation of OECs and ACs was enhanced by coculture with MG (56% +/- 16% and 85% +/- 13%, respectively). In contrast, SCs did not respond to any treatment or to costimulation by MG. Immunostaining for the chemokine Gro demonstrated a functional response that was consistent with NF kappaB activation. OECs expressed mRNA for Toll-like receptors (TLRs) 2 and 4, but only TLR4 protein was detected by Western blotting and immunohistochemistry. The results demonstrate that OECs possess the cellular machinery that permits them to respond to certain bacterial ligands, and may have an innate immune function in protecting the CNS against infection.
Vincent
Adele J
AJ
Department of Zoology, University of British Columbia, Vancouver, Canada. vincent@zoology.ubc.ca
Choi-Lundberg
Derek L
DL
Harris
Julie A
JA
West
Adrian K
AK
Chuah
Meng Inn
MI
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001424:Bacterial Infections / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000378:metabolism; D004927:Escherichia coli Infections / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D018836:Inflammation Mediators / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D009457:Neuroglia / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D009830:Olfactory Bulb / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D009832:Olfactory Nerve / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D018836:Inflammation Mediators; D016328:NF-kappa B; D051193:Toll-Like Receptors