The role of Toll-like receptor 4 in eliciting acquired immune responses against nontypeable Haemophilus influenzae following intranasal immunization with outer membrane protein.
OBJECTIVE
Acute otitis media (AOM) is one of the most common infectious diseases in children. Nontypeable Haemophilus influenzae (NTHi) is considered a major pathogen in AOM. Current treatment options depend mainly on the use of antibiotics, thus developing vaccines to prevent this disease is an urgent goal for public health. Outer membrane proteins (OMPs) are promising candidate targets for vaccination against NTHi.


METHODS
We used C3H/HeJ (Toll-like receptor 4 [TLR4]-mutant) mice, which arose spontaneously and have a non-functional TLR4 protein, and normal wild-type (WT) C3H/HeN mice. These mice were immunized intranasally with OMP from NTHi to investigate the mechanism of acquired immunity via TLR4. We examined the kinetics of mucosal and systemic antibody secretion and the migration of antibody producing lymphocytes to the mucosa in both strains during the course of intranasal immunization.


RESULTS
The mucosal and systemic immune responses against OMP from NTHi were elicited in both TLR4-mutant and WT mice. However, the mucosal IgA, and systemic IgG, and Th1 immune responses in WT mice were stronger than those in TLR4-mutant mice.


CONCLUSIONS
TLR4 plays an important role in relation to Th1 function for optimal development of the acquired immune responses to OMP administered intranasally. The variety of immune responses via TLR4 expression needs to be taken into consideration of individual vaccinations to prevent AOM.
Hirano
Takashi
T
Department of Otolaryngology, Faculty of Medicine, Oita University, Hasama-machi, Oita 8795593, Japan.
Kodama
Satoru
S
Moriyama
Munehito
M
Kawano
Toshiaki
T
Suzuki
Masashi
M
D000208:Acute Disease; D056704:Adaptive Immunity / Q000502:physiology; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D000917:Antibody Formation / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006193:Haemophilus influenzae / Q000276:immunology*; D007114:Immunization / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D010033:Otitis Media / Q000276:immunology* / Q000517:prevention & control; D011336:Probability; D011897:Random Allocation; D051197:Toll-Like Receptor 4 / Q000276:immunology* / Q000378:metabolism
D000907:Antibodies, Bacterial; D008565:Membrane Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D015847:Interleukin-4; D007371:Interferon-gamma