Open AccessMonophosphoryl lipid A induced innate immune responses via TLR 4 to enhance clearance of nontypeable H aemophilus influenzae and M oraxella catarrhalis from the nasopharynx in mice
Author(s) -
Hirano Takashi,
Kodama Satoru,
Kawano Toshiaki,
Maeda Kazuhiko,
Suzuki Masashi
Publication year - 2011
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1111/j.1574-695x.2011.00866.x
Subject(s) - moraxella catarrhalis , haemophilus influenzae , moraxella (branhamella) catarrhalis , microbiology and biotechnology , biology , immunology , innate immune system , immune system , pasteurellaceae , tlr4 , antibiotics
Acute otitis media ( AOM ) is one of the most common infectious diseases in children. Nontypeable H aemophilus influenzae ( NTH i) and M oraxella catarrhalis , G ram‐negative bacteria, are considered major pathogens of AOM and respiratory tract infections. In this study, we used monophosphoryl lipid A ( MPL ) as a Toll‐like receptor ( TLR 4) agonist to induce innate immune responses before challenge with NTH i and M . catarrhalis to enhance bacterial clearance from the nasopharynx. Mice were intranasally administered 40, 10, or 1 μg of MPL and challenged with NTH i and M . catarrhalis 12 and 24 h later. At 6 and 12 h after the bacterial challenge, the mice were killed and nasal washes were collected. The numbers of NTH i, M . catarrhalis , and inflammatory cells were quantitated. Inoculation of MPL produced a significant reduction in the number of bacteria recovered from the nasopharynx at 6 and/or 12 h after the bacterial challenge, when compared with control mice. The effect was dose dependent. MPL inoculation also induced the early accumulation of neutrophils in the nasopharynx after exposure to bacteria. MPL is effective for eliciting clearance of both NTH i and M . catarrhalis from the nasopharynx. These results indicate the possibility of a new strategy against G ram‐negative bacterial infection that involves the stimulation of the innate immune system by TLR 4 agonists such as MPL .