Stimulation of TLR7 prior to polymicrobial sepsis improves the immune control of the inflammatory response in adult mice.
OBJECTIVE
The role of Toll-like receptor 7 (TLR7), so far regarded as a receptor for viral RNA, was evaluated in a murine sepsis model.


METHODS
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Surgery, General Surgery, Visceral, Thoracical and Vascular Surgery, Ernst Moritz Arndt Universität, Friedrich-Loeffler-Str 23b, 17475 Greifswald, Germany. koernerp@uni-greifswald.de
P
P
Koerner
T
T
Traeger
H
H
Mehmcke
K
K
Cziupka
W
W
Kessler
A
A
Busemann
S
S
Diedrich
G
G
Hartmann
C-D
CD
Heidecke
S
S
Maier
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D012367:RNA, Viral / Q000276:immunology; D018805:Sepsis / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000276:immunology*
D016207:Cytokines; D007093:Imidazoles; D008070:Lipopolysaccharides; D012367:RNA, Viral; D051199:Toll-Like Receptor 7; C402365:resiquimod