Background: We previously showed that MyD88 knocked out mice were protected from death due to B. cenocepacia pneumonia implying that a toll-like receptor(s) (TLR) was involved in mediating death. The aim of the present study was to determine which TLR(s) was involved in triggering the inflammatory response responsible for the pathogenesis. We specifically focus on the TLRs 4 and 5, as these two receptors are the main ones involved in the recognition of P. aeruginosa, a flagellated Gram-bacterium similar to B. cenocepacia. Methods: Mice were infected intratracheally with a suspension of B. ceno-cepacia. Animals were then observed daily for signs of morbidity. Alternatively, bronchoalveolar lavages (BAL) were collected at different time points to further determine cytokine con-centrations and the number of CFU of B. ceno-cepacia. Results: The data clearly indicate that the innate immune response of the host to B. cenocepacia lung infection was due to TLR4 that senses the pathogen while TLR5 does not do so in vivo. As with the MyD88-/- strain, TLR4-/- mice were protected from death and cytokine and chemokine synthesis to infection were reduced. The only paradoxical observation was the reduced pathogen burden in the case of TLR4-/- mice compared to the enhanced (but transient) pathogen burden observed with MyD88-/- mice, suggesting that another TLR was involved in bacterial clearance. Conclusion: The data clearly demonstrate a deleterious implication of TLR4 in the host to B. cenocepacia lung infection.
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