Role for Toll-Like Receptor 2 in the Immune Response toStreptococcus pneumoniaeInfection in Mouse Otitis Media

Abstract

Streptococcus pneumoniaeis the most common pathogen associated with otitis media. To examine the role of Toll-like receptor 2 (TLR2) in host defense againstStreptococcus pneumoniaeinfection in the middle ear, wild-type (WT; C57BL/6) and TLR2-deficient (TLR2^−/−) mice were inoculated withStreptococcus pneumoniae(1 × 10⁶CFU) 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-κB, tumor necrosis factor alpha, interleukin 1β, MIP1α, 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.