The role of TLR2 in the host response to pneumococcal pneumonia in absence of the spleen.
BACKGROUND
Asplenic individuals are susceptible for overwhelming infection with Streptococcus pneumoniae, carrying a high mortality. Although Toll-like receptor (TLR)-2 is considered the major receptor for Gram-positive bacteria in innate immunity, it does not play a major role in host defense against pneumococcal pneumonia. We wanted to investigate if in absence of an intact spleen as a first line of defense, the role of TLR2 during pneumococcal pneumonia becomes more significant, thereby explaining its insignificant role during infections in immune competent hosts.


METHODS
We intranasally infected splenectomized wildtype (WT), TLR2 knock-out (KO) and TLR2/4 double KO mice with either serotype 2 or 3 S. pneumoniae.


RESULTS
There were no differences between asplenic WT and TLR2KO mice of bacterial loads in lung homogenates and blood, cytokine and chemokine levels in the lungs, and lung pathology scores. TLR2/4 double KO mice were not impaired in bacterial control as well, which indicates that besides the interaction between S. pneumoniae and TLR2, the interaction between pneumolysin and TLR4 does not stimulate antibacterial defense in the asplenic host either.


CONCLUSIONS
These results argue against a significant role of TLR2 in host defense during S. pneumoniae pneumonia in the asplenic state. Therefore, other components can provide sufficient backup mechanisms for TLR2 deficiency in the defense against intrapulmonary infections with S. pneumoniae of the otherwise immune competent host.
Center of Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. a.j.lammers@amc.uva.nl
Adriana J J
AJ
Lammers
Alexander P N A
AP
de Porto
Onno J
OJ
de Boer
Sandrine
S
Florquin
Tom
T
van der Poll
D000818:Animals; D058491:Bacterial Load; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011018:Pneumonia, Pneumococcal / Q000276:immunology*; D013154:Spleen / Q000002:abnormalities* / Q000276:immunology*; D013156:Splenectomy; D013296:Streptococcus pneumoniae / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4