Department of Surgery, General Surgery, Visceral, Thoracical and Vascular Surgery, Ernst Moritz Arndt Universität, Friedrich-Loeffler-Str 23b, 17475 Greifswald, Germany.
Inflamm Res. 2011 Mar;60(3):271-9. doi: 10.1007/s00011-010-0265-6. Epub 2010 Oct 17.
The role of Toll-like receptor 7 (TLR7), so far regarded as a receptor for viral RNA, was evaluated in a murine sepsis model.
We used the colon ascendens stent peritonitis model (CASP) in female C57B/6 mice. R-848 (1.5 μg/g body weight) was injected intravenously prior to sepsis induction.
We determined levels of cytokines by CBA detection kit. Different cell populations were isolated from the spleen by magnetic cell separation and the expression of TLR7 was visualized by immunofluorescence staining. Bacterial load of organs was quantified by incubating suspensions on agar in colony forming units.
R-848 application per se led to elevated cytokine levels in serum, spleen and peritoneal cavity. Expression of TLR7 on splenocytes was upregulated following CASP. Bacterial clearance in polymicrobial sepsis was significantly increased in spleen and peritoneum of mice pre-treated with the TLR7-agonist. Cytokine release was regulated in the peritoneum and spleen. Furthermore, apoptosis in thymus and spleen during polymicrobial sepsis was significantly decreased following TLR7 agonist application.
TLR7 seems to be essential for pathogen defence not only in viral but also in bacterial infections. Pharmacological stimulation of this receptor prior to induction of sepsis improves the host's capacity to cope with pathogens.
目前被认为是病毒 RNA 受体的 Toll 样受体 7（TLR7）在小鼠脓毒症模型中进行了评估。
我们使用雌性 C57B/6 小鼠的结肠升支支架腹膜炎模型（CASP）。在诱导脓毒症前，通过静脉内注射 R-848（1.5μg/g 体重）。
我们通过 CBA 检测试剂盒测定细胞因子水平。通过磁性细胞分离从脾脏中分离出不同的细胞群，并通过免疫荧光染色可视化 TLR7 的表达。通过在琼脂上孵育悬浮液来定量器官中的细菌负荷。
R-848 的应用本身导致血清、脾脏和腹腔中的细胞因子水平升高。在 CASP 后，脾细胞上的 TLR7 表达上调。在预先用 TLR7 激动剂处理的小鼠中，多微生物脓毒症中的脾脏和腹膜中的细菌清除率显著增加。细胞因子释放在腹膜和脾脏中得到调节。此外，多微生物脓毒症期间胸腺和脾脏中的细胞凋亡显著减少。
TLR7 似乎不仅在病毒感染中，而且在细菌感染中对病原体防御至关重要。在诱导脓毒症之前，该受体的药理学刺激可提高宿主应对病原体的能力。
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