Figure 1.

The role of triggering receptor expressed on myeloid cells-1 (TREM-1) signaling on the development of streptococcal toxic-shock-like syndrome (STSLS) caused by Streptococcus suis. (A) In the resting state, two reasons to confirm that TREM-1 signaling could not be activated by the surface actin on platelets: One reason is that TREM-1 expression is not induced; the other reason is that activation of TREM-1 on neutrophils by the surface actin on platelet requires the interaction of both cells, which is selectin/integrin dependent. Therefore, the signaling does not occur. (B) At the early stage of S. suis infection, TREM-1 expression is induced through various pattern-recognition receptors, such as toll-like receptor (TLR)2, TLR4, TLR6, and so on. The activated host cells could also secrete HMGB1 or peptidoglycan recognition protein 1 (PGLYRP1), which could serve as ligands for TREM-1 activation. In addition, the activated neutrophils could interact with platelets which could further provide surface actin for TREM-1 activation. The activation of TREM-1 signaling is essential for further activation of neutrophils and monocytes, which are important for bacterial clearance. At this stage, if S. suis could be significantly killed by these innate immune cells, the infection would be under control. (C) Severe infection would occur if the bacterial could resist the clearance. The Chinese epidemic S. suis strain has developed many strategies to resist the early killings, and the quick propagation of S. suis would provide more ligands for TLR activation to induce a significantly high level of TREM-1 expression. In addition, necrosis of host cells due to the infection of S. suis would provide much more ligands (such as actin and HMGB1) to activate TREM-1 signaling to cause severe inflammation. Ultimately, a TREM-1-mediated severe inflammatory response results in the cytokine storm, multiple organs failure, and high mortality—the characteristics of STSLS.