Role of Toll-like receptor 4 in innate immune responses in a mouse model of acute otitis media.
Nontypeable Haemophilus influenzae (NTHi) is considered a major pathogen underlying middle ear infection. This study characterized the role of Toll-like receptor 4 in the innate immune responses to acute otitis media induced by NTHi in mice. We used C3H/HeJ mice, which have nonfunctional Toll-like receptor 4, and normal wild-type C3H/HeN mice. NTHi were injected into the tympanic bulla, and middle ear effusions and tissues were collected. In C3H/HeN mice, the severity of acute otitis media decreased promptly with a significant reduction in bacterial recovery from middle ear effusions 48 h after injection. In contrast, all C3H/HeJ mice had otitis media at all time points examined, and increasing bacterial counts from middle ear effusions were detected in C3H/HeJ mice 72 h after injection. Expression of intracellular adhesion molecule-1 by the middle ear mucosa paralleled the number of polymorphonuclear cells in the middle ear in both strains. The findings of transmission electron microscopy revealed that phagocytosis and phagosome maturation of polymorphonuclear cells was impaired in C3H/HeJ mice. Our findings indicate that Toll-like receptor 4 plays a part in the early accumulation and functional promotion of polymorphonuclear cells in the middle ear for eradicating NTHi infection.
Hirano
Takashi
T
Department of Otolaryngology, Faculty of Medicine, Oita University, Oita, Japan.
Kodama
Satoru
S
Fujita
Keigo
K
Maeda
Kazuhiko
K
Suzuki
Masashi
M
D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D004432:Ear, Middle / Q000382:microbiology; D006192:Haemophilus Infections / Q000276:immunology*; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D018613:Microscopy, Confocal; D009504:Neutrophils / Q000276:immunology; D010033:Otitis Media / Q000276:immunology* / Q000382:microbiology; D051197:Toll-Like Receptor 4 / Q000276:immunology*
D051197:Toll-Like Receptor 4; D018799:Intercellular Adhesion Molecule-1