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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.* ; Stöger, T. ; Schiller, H. B. ; Sirard, J.C.* ; Le Bert, M.* ; Couillin, I.* ; Quesniaux, V.F.J.* ; Togbe, D.* ; Ryffel, B.*

Chronic Pseudomonas aeruginosa lung infection is IL-1R independent, but relies on MyD88 signaling.

Immunohorizons 5, 273-283 (2021)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 2573-7732
e-ISSN 2573-7732
Journal Immunohorizons
Quellenangaben Volume: 5, Issue: 5, Pages: 273-283 Article Number: , Supplement: ,
Publisher American Association of Immunologists
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)
German Center for Lung Research (DZL)