A critical role of Toll-like receptor 2 in chronic stress-induced immune suppression (P6309)

Abstract

Abstract Stress can enhance or suppress immune functions depending on the duration and severity of stressful situation. Our previous studies observed that Toll-like receptor (TLR) participates in chronic restraint stress-induced immune dysfunction. However, the mechanism by which TLR2 contributes to immune suppression induced by chronic restraint stress remains elusive. Our investigation found that stimulation of TLR2 by peptidoglycan (PGN), a TLR2 ligand, significantly attenuates cell apoptosis in splenocytes induced by chronic restraint stress. Furthermore, we found that administration of PGN markedly blocks chronic restraint stress-induced alterations of anti-apoptotic and apoptotic genes, including Bcl/2 and glycogen synthase kinase-3β (GSK-3β). We also found that activation of TLR2 by PGN inhibits chronic stress-reduced level of c-Jun N-terminal kinase (JNK) phosphorylation. This effect of PGN is abolished in TLR2 deficient mice, suggesting PGN-induced protection of JNK phosphorylation through a TLR2 dependent manner. Moreover, our data have shown that chronic stress caused a dramatic decrease in cytokine IL-2 level but an increase in the cytokines IL-4 and IL-17 in CD4+ T cells. Interestingly, stimulation of TLR2 by PGN could block these alterations of cytokine levels induced by chronic stress. Collectively, our studies thus demonstrate that stimulation of TLR2 attenuates chronic stress-induced immune suppression by modulating apoptosis-related proteins and cytokines.