Toll-like receptor 2 deficiency relieves splenic immunosuppression during sepsis

Immunosuppression is associated with long-term mortality during sepsis. However, the underlying mechanism of immunosuppression remains poorly understood. Toll-like receptor 2 (TLR2) contributes to sepsis pathogenesis. We sought to determine the role of TLR2 in immunosuppression in the spleen during polymicrobial sepsis. Using an experimental model of polymicrobial sepsis induced by cecal ligation and puncture (CLP), we measured the expression of inflammatory cytokines and chemokines in spleen 6 and 24 h after CLP to evaluate the immune response, and compared the expression of inflammatory cytokines and chemokines, apoptosis, and intracellular ATP production in spleen of wild-type (WT) and TLR2-deficient (TLR2-/-) mice 24 h after CLP. We found that pro-inflammatory cytokines and chemokines, such as TNF-alpha and IL-1 beta peaked 6 h after CLP, while IL-10, an anti-inflammatory cytokine, peaked 24 h after CLP in the spleen. At this later time point, TLR2-/-mice presented decreased levels of IL-10 and decreased caspase 3 activation but no significant difference in intracellular ATP production in spleen compared to WT mice. Our data imply that TLR2 has a pronounced effect on sepsis-induced immunosuppression in spleen.