Toll-Like Receptor 2 Deficiency Increases Resistance to Pseudomonas aeruginosa Pneumonia in the Setting of Sepsis-Induced Immune Dysfunction

作者：Pene Frederic; Grimaldi David; Zuber Benjamin; Sauneuf Bertrand; Rousseau Christophe; El Hachem Carole; Martin Clemence; Belaidouni Nadia; Balloy Viviane; Mira Jean Paul; Chiche Jean Daniel^*

来源：Journal of Infectious Diseases, 2012, 206(6): 932-942.

DOI：10.1093/infdis/jis438

Background. Sepsis is characterized by a dysregulated inflammatory response followed by immunosuppression that favors the development of secondary infections. Toll-like receptors (TLRs) are major regulators of the host%26apos;s response to infections. How variability in TLR signaling may impact the development of sepsis-induced immune dysfunction has not been established. We sought to establish the role of TLR2, TLR4, and TLR5 in postseptic mice with Pseudomonas aeruginosa pneumonia. %26lt;br%26gt;Methods. We used an experimental model of sublethal polymicrobial sepsis induced by cecal ligation and puncture (CLP). Wild-type, tlr2(-/-), tlr4(-/-), tlr5(-/-), tlr2 x 4(-/-) mice that underwent CLP were secondarily subjected to P. aeruginosa pulmonary infection. %26lt;br%26gt;Results. Postseptic wild-type and tlr4(-/-) and tlr5(-/-) mice displayed high susceptibility to P. aeruginosa pneumonia. In contrast, TLR2-deficient mice, either tlr2(-/-)or tlr2 x 4(-/-), that underwent CLP were resistant to the secondary pulmonary infection. As compared to wild-type mice, tlr2(-/-) mice displayed improvement in bacterial clearance, decreased bacteremic dissemination, and attenuated lung damage. Furthermore, tlr2(-/-) mice exhibited a pulmonary proinflammatory cytokine balance, with increased production of tumor necrosis factor alpha and decreased release of interleukin 10. %26lt;br%26gt;Conclusions. In a model of secondary P. aeruginosa pneumonia in postseptic mice, TLR2 deficiency improves survival by promoting efficient bacterial clearance and restoring a proinflammatory cytokine balance in the lung.

• 出版日期2012-9-15