Stimulation of TLR7 prior to polymicrobial sepsis improves the immune control of the inflammatory response in adult mice
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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.
KeywordsCASP Toll like receptor R-848 Resiquimod Sepsis
We thank Kathrin Mülling and Antje Janetzko for excellent technical assistance and Robert Jack for critical reading of the manuscript. Hendrik Mehmcke was supported in the graduate school GRK 840 (Host-pathogen interactions) by a predoctoral fellowship from Deutsche Forschungsgemeinschaft (DFG).
Conflict of interest
No conflicts of interest exist.