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Infection and Immunity, July 2009, p. 3100-3108, Vol. 77, No. 7
0019-9567/09/$08.00+0     doi:10.1128/IAI.00204-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Role for Toll-Like Receptor 2 in the Immune Response to Streptococcus pneumoniae Infection in Mouse Otitis Media

Fengchan Han,¹ Heping Yu,¹ Cong Tian,¹ Shengli Li,¹ Michael R. Jacobs,² Cindy Benedict-Alderfer,¹ and Qing Y. Zheng^1*

Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, Ohio 44106,¹ Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106²

Received 22 February 2009/ Returned for modification 8 April 2009/ Accepted 21 April 2009

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 10⁶ 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-B, tumor necrosis factor alpha, interleukin 1β, MIP1, 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.

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* Corresponding author. Mailing address: Department of Otolaryngology-HNS, Case Western Reserve University, 11100 Euclid Avenue, LKS 5045, Cleveland, OH 44106. Phone: (216) 844-3441. Fax: (216) 844-7268. E-mail: qing.zheng{at}case.edu

Published ahead of print on 4 May 2009.

Editor: A. Camilli

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Infection and Immunity, July 2009, p. 3100-3108, Vol. 77, No. 7
0019-9567/09/$08.00+0     doi:10.1128/IAI.00204-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.