The role of DNA sensing and innate immune receptor TLR9 in otitis media.
Otitis media (OM), a common infectious disease in children, is associated with bacterial middle ear (ME) infection. Toll-like receptors (TLRs) are important mediators of innate immune responses, and TLR9 specifically recognizes the unmethylated cytidine-phosphate-guanosine (CpG) motifs in bacterial DNA. Additional sensors of foreign DNA have recently been identified. The role of DNA sensing and TLR9 was investigated in a murine model of OM induced by non-typeable Haemophilus influenzae (NTHi). Expression of genes related to DNA-sensing pathways involved in innate immunity was assessed via DNA microarray, qPCR and immunohistochemistry. Middle ear responses to NTHi were examined in wild-type and TLR9(-/-) mice by histopathology and bacterial culture. Expression of TLR9 signaling genes was modestly up-regulated during OM, as was TLR9 protein in both ME mucosal cells and infiltrating leukocytes. However, genes known to be regulated by CpG DNA were dramatically up-regulated, as were genes involved in DNA sensing by DIA, Pol-III and AIM2. Toll-like receptor 9 deletion significantly prolonged the inflammatory response induced by NTHi in the ME and delayed bacterial clearance. The results suggest that DNA sensing via TLR9 plays a role in OM pathogenesis and recovery. Alternative forms of DNA sensing may also contribute to OM.
Department of Surgery/Otolaryngology, University of Lübeck, Lübeck, Germany.
Anke
A
Leichtle
Michelle
M
Hernandez
Jasmine
J
Lee
Kwang
K
Pak
Nicholas J
NJ
Webster
Barbara
B
Wollenberg
Stephen I
SI
Wasserman
Allen F
AF
Ryan
D000818:Animals; D018899:CpG Islands / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004269:DNA, Bacterial / Q000378:metabolism*; D004195:Disease Models, Animal; D004432:Ear, Middle / Q000473:pathology; D005786:Gene Expression Regulation; D006192:Haemophilus Infections / Q000276:immunology*; D006193:Haemophilus influenzae; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046228:Microarray Analysis; D009092:Mucous Membrane / Q000276:immunology / Q000473:pathology; D010033:Otitis Media / Q000276:immunology* / Q000382:microbiology; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D016207:Cytokines; D004269:DNA, Bacterial; D051217:Toll-Like Receptor 9
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