Toll-like receptor 4 is critical to innate host defense in a murine model of bordetellosis

Bordetellae are important respiratory pathogens that cause pertussis (whooping cough) in humans and analogous diseases in domestic and wild animals. Immunity to Bordetella is poorly understood, in particular the early innate immune responses that contribute to inflammation, pathology, and the subsequent generation of adaptive immunity. Using B. bronchiseptica, which naturally infects mice, we show that Toll-like receptor-4 (TLR4) is required for cytokine responses to this pathogen's lipopolysaccharide (LPS) and that TLR4 deficiency results in impaired cytokine responses in vitro and in vivo. TLR4-deficient mice rapidly succumb following inoculation with as few as 1000 organisms, indicating that TLR4 is critical to innate host defense against bordetellosis.