Chronic Pseudomonas aeruginosa lung infection is IL-1R independent, but relies on MyD88 signaling (CROSBI ID 309437)
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Mackowiak, Claire ; Marchiol, Tiffany ; Čipčić Paljetak, Hana ; Fauconnier, Louis ; Palomo, Jennifer ; Secher, Thomas ; Panek, Corinne ; Sedda, Delphine ; Savigny, Florence ; Erard, Francois ; Bragonzi, Alessandra ; Huaux, Francois ; Stoeger, Tobias ; Schiller, Herbert B. ; Sirard, Jean-Claude ; Le Bert, Marc ; Couillin, Isabelle ; Quesniaux, Valerie F. J. ; Togbe, Dieudonnée ; Ryffel, Bernhard
engleski
Chronic Pseudomonas aeruginosa lung infection is IL-1R independent, but relies on MyD88 signaling
Cystic fibrosis is associated with chronic Pseudomonas aeruginosa colonization and inflammation. The role of MyD88, the shared adapter protein of the proinflammatory TLR and IL- 1R families, in chronic P. aeruginosa biofilm lung infection is unknown. We report that chronic lung infection with the clinical P. aeruginosa RP73 strain is associated with uncontrolled lung infection in complete MyD88-deficient mice with epithelial damage, inflammation, and rapid death. Then, we investigated whether alveolar or myeloid cells contribute to heightened sensitivity to infection. Using cell-specific, MyD88-deficient mice, we uncover that the MyD88 pathway in myeloid or alveolar epithelial cells is dispensable, suggesting that other cell types may control the high sensitivity of MyD88-deficient mice. By contrast, IL-1R1-deficient mice control chronic P. aeruginosa RP73 infection and IL-1β Ab blockade did not reduce host resistance. Therefore, the IL- 1R1/MyD88 pathway is not involved, but other IL-1R or TLR family members need to be investigated. Our data strongly suggest that IL-1 targeted neutralizing therapies used to treat inflammatory diseases in patients unlikely reduce host resistance to chronic P. aeruginosa infection.
Pseudomonas aeruginosa ; chronic lung infection ; MyD88 signaling
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