TY  - JOUR
AB  - 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.
AU  - Mackowiak, C.*
AU  - Marchiol, T.*
AU  - Paljetak, H.C.*
AU  - Fauconnier, L.*
AU  - Palomo, J.*
AU  - Secher, T.*
AU  - Panek, C.*
AU  - Sedda, D.*
AU  - Savigny, F.*
AU  - Erard, F.*
AU  - Bragonzi, A.*
AU  - Huaux, F.*
AU  - Stöger, T.
AU  - Schiller, H. B.
AU  - Sirard, J.C.*
AU  - Le Bert, M.*
AU  - Couillin, I.*
AU  - Quesniaux, V.F.J.*
AU  - Togbe, D.*
AU  - Ryffel, B.*
C1  - 61931
C2  - 50519
SP  - 273-283
TI  - Chronic Pseudomonas aeruginosa lung infection is IL-1R independent, but relies on MyD88 signaling.
JO  - Immunohorizons
VL  - 5
IS  - 5
PY  - 2021
SN  - 2573-7732
ER  -