title: Toll-like receptors 2 and 3 agonists differentially affect oligodendrocyte survival, differentiation, and myelin membrane formation.
abstract: Toll-like receptors (TLRs) play a key role in controlling innate immune responses to a wide variety of pathogen-associated molecules as well as endogenous signals. In addition, TLR expression within nonimmune cells has been recognized as as modulator of cell behavior. In this study we have addressed the question of whether functional TLRs are expressed on oligodendrocytes, the myelinating cells of the central nervous system. Primary cultures of rat oligodendrocytes at different maturation stages were found to express TLR2 and, to lesser extent, TLR3. Immunocytochemical analysis revealed that both TLRs were localized at the cell body and primary processes and were excluded from myelin-like membranes. Interestingly, innate immune receptor ligands were able to modulate oligodendrocyte survival, differentiation, and myelin-like membrane formation, indicating that TLRs on oligodendrocytes are functional. In highly purified oligodendrocytes cultures, the TLR2 agonist zymosan promoted survival, differentiation, and myelin-like membrane formation, whereas poly-I:C, a TLR3 ligand, was a potent inducer of apoptosis. Together, these data indicate that, in addition to other neural cell types, also oligodendrocytes express functional TLRs, which play a role in regulating various aspects of oligodendrocyte behavior.
authors.affiliation: Delta Crystallon BV, Leiden, The Netherlands.
authors.forename: Malika
authors.initials: M
authors.lastname: Bsibsi
authors.forename: Anita
authors.initials: A
authors.lastname: Nomden
authors.forename: Johannes M
authors.initials: JM
authors.lastname: van Noort
authors.forename: Wia
authors.initials: W
authors.lastname: Baron
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D009186:Myelin Sheath / Q000187:drug effects / Q000502:physiology*; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D051195:Toll-Like Receptor 2 / Q000819:agonists* / Q000502:physiology*; D051196:Toll-Like Receptor 3 / Q000819:agonists* / Q000502:physiology*; D015054:Zymosan / Q000494:pharmacology
chemical_list: C530472:TLR3 protein, rat; C495343:Tlr2 protein, rat; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D015054:Zymosan