Toll-like receptor 2 and facial motoneuron survival after facial nerve axotomy.
We have previously demonstrated that CD4(+) Th2 lymphocytes are required to rescue facial motoneuron (FMN) survival after facial nerve axotomy through interaction with peripheral antigen presenting cells, as well as CNS resident microglia. Furthermore, the innate immune molecule, toll-like receptor 2 (TLR2), has been implicated in the development of Th2-type immune responses and can be activated by intracellular components released by dead or dying cells. The role of TLR2 in the FMN response to axotomy was explored in this study, using a model of facial nerve axotomy at the stylomastoid foramen in the mouse, in which blood-brain-barrier (BBB) permeability does not occur. After facial nerve axotomy, TLR2 mRNA was significantly upregulated in the facial motor nucleus and co-immunofluorescence localized TLR2 to CD68(+) microglia, but not GFAP(+) astrocytes. Using TLR2-deficient (TLR2(-/-)) mice, it was determined that TLR2 does not affect FMN survival levels after axotomy. These data contribute to understanding the role of innate immunity after FMN death and may be relevant to motoneuron diseases, such as amyotrophic lateral sclerosis (ALS).
Wainwright
Derek A
DA
Dept. of Cell Biology, Neurobiology, and Anatomy, Loyola University Medical Center, Maywood, IL 60153, United States. dwainwr@surgery.bsd.uchicago.edu
Xin
Junping
J
Mesnard
Nichole A
NA
Sanders
Virginia M
VM
Jones
Kathryn J
KJ
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism; D019771:Axotomy; D002470:Cell Survival; D005154:Facial Nerve / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D009046:Motor Neurons / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D018418:Th2 Cells / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; C528900:glial fibrillary astrocytic protein, mouse