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Chronic Pseudomonas aeruginosa Lung Infection Is IL-1R Independent, but Relies on MyD88 Signaling

Abstract : 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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https://hal.inrae.fr/hal-03258180
Contributor : Jean-Claude Sirard <>
Submitted on : Friday, June 11, 2021 - 3:55:50 PM
Last modification on : Saturday, September 18, 2021 - 3:19:12 AM

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Distributed under a Creative Commons Attribution - NonCommercial - NoDerivatives 4.0 International License

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Claire Mackowiak, Tiffany Marchiol, Hana Cipcic Paljetak, Louis Fauconnier, Jennifer Palomo, et al.. Chronic Pseudomonas aeruginosa Lung Infection Is IL-1R Independent, but Relies on MyD88 Signaling. ImmunoHorizons , The American Association of Immunologists, Inc, 2021, 5 (5), pp.273-283. ⟨10.4049/immunohorizons.2000095⟩. ⟨hal-03258180⟩

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