TY - JOUR
T1 - Toll-Like Receptor 2 Mediates In Vivo Pro- and Anti-inflammatory Effects of Mycobacterium Tuberculosis and Modulates Autoimmune Encephalomyelitis
AU - Piermattei, Alessia
AU - Migliara, Giuseppe
AU - Di Sante, Gabriele
AU - Foti, Maria
AU - Hayrabedyan, Soren Bohos
AU - Papagna, Angela
AU - Geloso, Maria Concetta
AU - Corbi, Maddalena
AU - Valentini, Mariagrazia
AU - Sgambato, Alessandro
AU - Delogu, Giovanni
AU - Constantin, Gabriela
AU - Ria, Francesco
PY - 2016
Y1 - 2016
N2 - Mycobacteria display pro- and anti-inflammatory effects in human and experimental pathology. We show here that both effects are mediated by Toll-like receptor 2 (Tlr2), by exploiting a previously characterized Tlr2 variant (Met82Ile). Tlr2 82ile promoted self-specific proinflammatory polarization as well as expansion of ag-specific FoxP3+ Tregs, while Tlr2 82met impairs the expansion of Tregs and reduces the production of IFN-γ and IL-17 proinflammatory cytokines. Preferential dimerization with Tlr1 or Tlr6 could not explain these differences. In silico, we showed that Tlr2 variant Met82Ile modified the binding pocket for peptidoglycans and participated directly to a putative binding pocket for sugars and cadherins. The distinct pro- and anti-inflammatory actions impacted severity, extent of remission, and distribution of the lesions within the central nervous system of experimental autoimmune encephalomyelitis. Thus, Tlr2 has a janus function in vivo as mediator of the role of bacterial products in balancing pro- and anti-inflammatory immune responses.
AB - Mycobacteria display pro- and anti-inflammatory effects in human and experimental pathology. We show here that both effects are mediated by Toll-like receptor 2 (Tlr2), by exploiting a previously characterized Tlr2 variant (Met82Ile). Tlr2 82ile promoted self-specific proinflammatory polarization as well as expansion of ag-specific FoxP3+ Tregs, while Tlr2 82met impairs the expansion of Tregs and reduces the production of IFN-γ and IL-17 proinflammatory cytokines. Preferential dimerization with Tlr1 or Tlr6 could not explain these differences. In silico, we showed that Tlr2 variant Met82Ile modified the binding pocket for peptidoglycans and participated directly to a putative binding pocket for sugars and cadherins. The distinct pro- and anti-inflammatory actions impacted severity, extent of remission, and distribution of the lesions within the central nervous system of experimental autoimmune encephalomyelitis. Thus, Tlr2 has a janus function in vivo as mediator of the role of bacterial products in balancing pro- and anti-inflammatory immune responses.
KW - EAE/MS
KW - Foxp3
KW - EAE/MS
KW - Foxp3
UR - http://hdl.handle.net/10807/94211
U2 - 10.3389/fimmu.2016.00191
DO - 10.3389/fimmu.2016.00191
M3 - Article
SN - 1664-3224
SP - N/A-N/A
JO - Frontiers in Immunology
JF - Frontiers in Immunology
ER -