047 - Lack of MyD88 protects the immunodeficient host against fatal lung inflammation triggered by the opportunistic bacteria Burkholderia cenocepacia - 05/12/08
G. Ventura [1 et 2],
V. Balloy [1 et 2],
M. Huerre [3],
MC. Plotkowski [4],
M. Chignard [1 et 2],
M. Si-Tahar [1 et 2]
Voir les affiliationsIntroduction: Burkholderia cenocepacia is an opportunistic pathogen of major concern for cystic fibrosis patients as well as immunocompromised cancer patients and transplant recipients. The mechanisms by which B cenocepacia triggers a rapid health deterioration of the susceptible host have yet to be characterized. Toll-like receptors (TLR) and their key signaling intermediate myeloid differentiation (MyD)88 play a central role in the detection of microbial molecular patterns and in the initiation of an effective immune response. Here, we designed an investigation to better understand the role of TLR-MyD88 signaling in B cenocepacia-induced pathogenesis in the immunocompromized host, using an experimental murine model.
Methodology: The time-course of several dynamic parameters, including animal survival, bacterial load and secretion of critical inflammatory mediators, was compared in infected and immunosuppressed wild-type and MyD88-/- mice.
Results: When compared to wild-type mice, infected MyD88-/- animals displayed significantly reduced levels of inflammatory mediators (including KC, TNF, IL-6, MIP-2 and G-CSF) in blood and lung airspaces. Moreover, despite a higher transient bacterial load in the lungs, immunosuppressed mice deficient in MyD88 had an unexpected survival advantage. Finally, we showed that this B cenocepacia-induced life-threatening infection of wild- type mice could be prevented by corticosteroids.
Conclusions: Our findings demonstrate that a MyD88-dependent pathway can critically contribute to a detrimental host inflammatory response that leads to fatal pneumonia.
© 2008 Elsevier Masson SAS. Tous droits réservés.
Vol 25 - N° 9
P. 1179 - novembre 2008 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.