Toll-like receptors (TLRs) orchestrate immune responses to a wide variety of danger- and pathogen-associated molecular patterns. Compared to the central nervous system (CNS), expression profile and function of TLRs in the human peripheral nervous system (PNS) are ill-defined. We analyzed TLR expression of satellite glial cells (SGCs) and microglia, glial cells predominantly involved in local immune responses in ganglia of the human PNS and normal-appearing white matter (NAWM) of the CNS, respectively. Ex vivo flow cytometry analysis of cell suspensions obtained from human cadaveric trigeminal ganglia (TG) and NAWM showed that both SGCs and microglia expressed TLR1-5, TLR7, and TLR9, although expression levels varied between these cell types. Immunohistochemistry confirmed expression of TLR1-TLR4 and TLR9 by SGCs in situ. Stimulation of TG- and NAWM-derived cell suspensions with ligands of TLR1-TLR6, but not TLR7 and TLR9, induced interleukin 6 (IL-6) secretion. We identified CD45LOWCD14POS SGCs and microglia, but not CD45HIGH leukocytes and CD45NEG cells as the main source of IL-6 and TNF-α upon stimulation with TLR3 and TLR5 ligands. In conclusion, human TG-resident SGCs express a broad panel of functional TLRs, suggesting their role in initiating and orchestrating inflammation to pathogens in human sensory ganglia.

Additional Metadata
Keywords Cytokines, Human trigeminal ganglion, Microglia, Satellite glial cell, Toll-like receptor
Persistent URL dx.doi.org/10.1002/eji.201746989, hdl.handle.net/1765/100291
Journal European Journal of Immunology
Citation
Mitterreiter, J.G, Ouwendijk, W.J.D, van Velzen, M. (Monique), van Nierop, G.P, Osterhaus, A.D.M.E. (Albert D. M. E.), & Verjans, G.M.G.M. (2017). Satellite glial cells in human trigeminal ganglia have a broad expression of functional Toll-like receptors. European Journal of Immunology, 47(7), 1181–1187. doi:10.1002/eji.201746989