Toll-like receptor 9 acts at an early stage in host defence against pneumococcal infection.
Toll-like receptor 9 (TLR9) induces an inflammatory response by recognition of unmethylated CpG dinucleotides, mainly present in prokaryotic DNA. So far, TLR9-deficient mice have been shown to be more sensitive than wild-type mice to viral, but not to bacterial infections. Here, we show that mice deficient in TLR9 but not in TLR1, TLR2, TLR4 and TLR6 or IL-1R/IL-18R are more susceptible to a respiratory tract bacterial infection caused by Streptococcus pneumoniae. Intranasal challenge studies revealed that TLR9 plays a protective role in the lungs at an early stage of infection prior to the entry of circulating inflammatory cells. Alveolar as well as bone marrow-derived macrophages deficient in either TLR9 or the myeloid adaptor differentiation protein MyD88 were impaired in pneumococcal uptake and in pneumococcal killing. Our data suggest that in the airways, pneumococcal infection triggers a TLR9 and MyD88-dependent activation of phagocytic activity from resident macrophages leading to an early clearance of bacteria from the lower respiratory tract.
Albiger
Barbara
B
Swedish Institute for Infectious Disease Control and Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 18, SE-171 82 Solna, Sweden. Barbara.Albiger@med.lu.se
Dahlberg
Sofia
S
Sandgren
Andreas
A
Wartha
Florian
F
Beiter
Katharina
K
Katsuragi
Hiroaki
H
Akira
Shizuo
S
Normark
Staffan
S
Henriques-Normark
Birgitta
B
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D010587:Phagocytosis; D011008:Pneumococcal Infections / Q000276:immunology* / Q000382:microbiology; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000502:physiology; D051194:Toll-Like Receptor 1 / Q000235:genetics / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000502:physiology; D051216:Toll-Like Receptor 6 / Q000235:genetics / Q000502:physiology; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000502:physiology*
D017472:Receptors, Interleukin-1; C495345:TLR4 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D051217:Toll-Like Receptor 9