Targeting TREM-1 Signaling in the Presence of Antibiotics is Effective Against Streptococcal Toxic-Shock-Like Syndrome (STSLS) Caused by Streptococcus suis.
Targeting TREM-1 Signaling in the Presence of Antibiotics is Effective Against Streptococcal Toxic-Shock-Like Syndrome (STSLS) Caused by Streptococcus suis.
复制标题
在抗生素存在下靶向 TREM-1 信号传导可有效对抗猪链球菌引起的链球菌中毒性休克样综合征 (STSLS)
DOI：
10.3389/fcimb.2015.00079
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发表时间：
2015
影响因子：
5.7
通讯作者：
Zhang A
中科院分区：
文献类型：
--
作者：
Yang C;Zhao J;Lin L;Pan S;Fu L;Han L;Jin M;Zhou R;Zhang A
猪链球菌（S.suis）是一种主要的猪病原体，也是对人类健康的严重威胁。感染高毒力猪链球菌菌株可引起人链球菌中毒性休克样综合征（STSLS），这与血清促炎细胞因子水平高和死亡率高有关。我们之前的研究表明，高毒力的猪链球菌感染可以激活TREM-1信号通路，促进宿主在感染早期清除猪链球菌。然而，在抗生素存在的情况下，TREM-1信号是否可以作为STSLS的靶点仍有待研究。在本研究中，小鼠被一种高毒力猪链球菌感染，然后用rTREM-1 （TREM-1的重组细胞外结构域）处理，阻断TREM-1信号通路、抗生素（包括rTREM-1和抗生素）或PBS。观察生存率、临床体征、血清IL-1β、TNF-α水平及血清细菌载量。如前所述，用rTREM-1治疗可能加重感染的结果。虽然传统的抗生素治疗有助于有效的猪链球菌清除，但它并没有显著提高生存率。相比之下，由于过度的促炎反应减少，rTREM-1联合抗生素治疗不仅能有效清除细菌，还能减轻炎症。综上所述，TREM-1信号有助于严重的炎症反应，并有利于猪链球菌的清除。因此，在抗生素存在的情况下，阻断TREM-1信号仍然可能是治疗STSLS的靶点。
Streptococcus suis (S.suis), a major swine pathogen, is also a severe threat to human health. Infection with highly virulent strains of S. suis can cause human Streptococcal toxic-shock-like syndrome (STSLS), which is associated with high serum pro-inflammatory cytokine levels and a high mortality rate. Our previous study indicated that highly virulent S. suis infection could activate the TREM-1 signaling pathway, which promotes host clearance of S. suis during early infection. However, it remained to be elicited whether TREM-1 signaling could be a target against STSLS in the presence of antibiotic. In the present study, mice were infected with a highly virulent S. suis strain and then treated with rTREM-1 (the recombinant extracellular domain of TREM-1) to block TREM-1 signaling, antibiotics, both rTREM-1 and antibiotics, or PBS. The survival rates, clinical signs, serum IL-1β and TNF-α levels, and serum bacterial loads were evaluated. Treatment with rTREM-1 could aggravate the outcome of infection as described previously. Although the conventional treatment with antibiotics contributed to effective S. suis clearance, it did not improve survival significantly. In comparison, due to the reduction of the exaggerated pro-inflammatory response, treatment combined with rTREM-1 and antibiotics not only led to efficient bacterial clearance but also alleviated inflammation. In conclusion, TREM-1 signaling contributed to severe inflammatory response and benefited S. suis clearance. Therefore, blocking TREM-1 signaling could still be a target for the treatment of STSLS in the presence of antibiotics.