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.
- Mackowiak, C.
- Marchiol, T.
- Paljetak, H. C.
- Fauconnier, L.
- Palomo, J.
- Secher, T.
- Panek, C.
- Sedda, D.
- Savigny, F.
- Erard, F.
- Bragonzi, A.
- Huaux, F.
- Stoeger, T.
- Schiller, H. B.
- Sirard, J. C.
- Le Bert, M.
- Couillin, I.
- Quesniaux, V. F. J.
- Togbe, D.
- Ryffel, B.
