Abstract
As shown in a previous study (Ventura et al., 2009), MyD88, a key downstream adapter for most of the TLRs, is involved in the inflammatory response responsible to the death due to B. cenocepacia pneumonia.
The aim of the present study was to determine which TLRs were involved in this response. We specifically focused on the TLRs 4 and 5, as these two receptors are the main ones involved in the recognition of P. aeruginosa, a flagellated Gram-negative bacterium like B. cenocepacia.
Mice deficient for TLR4, TLR5 or both were infected intratracheally with a suspension of B. cenocepacia and animal survival was observed daily. Alternatively, bronchoalveolar lavages were collected at different time points to further determine cytokine concentrations and the number of CFU of B. cenocepacia.
We observed that the inflammatory response of the host to B. cenocepacia lung infection was due to TLR4 and not to TLR5. As for the MyD88-/- strain, TLR4-/- mice were protected from death and cytokine and chemokine synthesis in response to infection were reduced. By contrast, we observed a 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.
The data clearly demonstrate a detrimental role of TLR4 for the host upon B. cenocepacia lung infection.
Reference:
1. Ventura et al., J Immunol. 2009;183:670-6.
- © 2011 ERS