Response of Toll-like receptors in experimental Guillain–Barré syndrome: A kinetic analysis

Guillain–Barré syndrome (GBS) is an autoimmune disorder caused by the interaction between cellular and humoral immune responses in the peripheral nervous system. Toll-like receptors (TLRs) are key players in innate and have regulatory functions in adaptive immunity. In this study, we systematically examined expression patterns of TLRs in sciatic nerve and lymphoid organs during the disease course of murine experimental autoimmune neuritis and in blood from Guillain–Barré patients. A kinetic response pattern was identified, characterized by a pronounced up-regulation of TLR2, 6 and 11 on T cells and TLR4 and 6 on APCs, while TLR1 expression was decreased. Moreover, an enhanced expression of the disease promoting cytokine Interleukin-(IL)17A was detected. Additional analysis of GBS patients revealed an up-regulation of TLR2, TLR4 and TLR6 mRNA, negatively correlated with disease severity. This first systematic analysis of TLR expression pattern may contribute to elucidating the role of TLRs in GBS pathophysiology.

► TLR2/6 is significantly increased on T cells and APCs, in sciatic nerve infiltrates of EAN mice and in blood of GBS patients.
► TLR4 is highly significant up-regulated on MHCII+ cells, in sciatic nerve infiltrates of EAN mice and in blood of GBS patients.
► TLR1 is significantly down-regulated in the induction phase on T cells and APCs.
► TLR11 expression is augmented on CD4+ T cells during EAN progression.
► MyD88 and IL-17A expression is enhanced on T cells in EAN mice.