Role for Toll-like receptor 2 in the immune response to Streptococcus pneumoniae infection in mouse otitis media.
Streptococcus pneumoniae is the most common pathogen associated with otitis media. To examine the role of Toll-like receptor 2 (TLR2) in host defense against Streptococcus pneumoniae infection in the middle ear, wild-type (WT; C57BL/6) and TLR2-deficient (TLR2(-/-)) mice were inoculated with Streptococcus pneumoniae (1 x 10(6) CFU) through the tympanic membrane. Nineteen of 37 TLR2(-/-) mice showed bacteremia and died within 3 days after the challenge, compared to only 4 of 32 WT mice that died. Of those that survived, more severe hearing loss in the TLR2(-/-) mice than in the WT mice was indicated by an elevation in auditory-evoked brain stem response thresholds at 3 or 7 days postinoculation. The histological pathology was characterized by effusion and tissue damage in the middle ear, and in the TLR2(-/-) mice, the outcome of infection became more severe at 7 days. At both 3 and 7 days postchallenge, the TLR2(-/-) mice had higher blood bacterial titers than the WT mice (P < 0.05), and typical bacteria were identified in the effusion from both ears of both mouse groups by acridine orange staining. Moreover, by 3 days postchallenge, the mRNA accumulation levels of NF-kappaB, tumor necrosis factor alpha, interleukin 1beta, MIP1alpha, Muc5ac, and Muc5b were significantly lower in the ears of TLR2(-/-) mice than in WT mice. In summary, TLR2(-/-) mice may produce relatively low levels of proinflammatory cytokines following pneumococcal challenge, thus hindering the clearance of bacteria from the middle ear and leading to sepsis and a high mortality rate. This study provides evidence that TLR2 is important in the molecular pathogenesis and host response to otitis media.
Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Fengchan
F
Han
Heping
H
Yu
Cong
C
Tian
Shengli
S
Li
Michael R
MR
Jacobs
Cindy
C
Benedict-Alderfer
Qing Y
QY
Zheng
D000818:Animals; D016470:Bacteremia / Q000276:immunology; D015169:Colony Count, Microbial; D005260:Female; D034381:Hearing Loss / Q000276:immunology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010033:Otitis Media / Q000276:immunology* / Q000382:microbiology*; D011008:Pneumococcal Infections / Q000150:complications / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D016019:Survival Analysis; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000276:immunology*
C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2