铜绿假单胞菌
炎症
促炎细胞因子
囊性纤维化
免疫学
慢性感染
肺
生物
封锁
髓样
免疫系统
微生物学
医学
受体
细菌
内科学
生物化学
遗传学
作者
Claire Mackowiak,Tiffany Marchiol,Hana Čipčić Paljetak,Louis Fauconnier,Jennifer Palomo,Thomas Sécher,Corinne Panek,Delphine Sedda,Florence Savigny,François Erard,Alessandra Bragonzi,François Huaux,Tobias Stoeger,Herbert B. Schiller,Jean‐Claude Sirard,Marc Le Bert,Isabelle Couillin,Valérie Quesniaux,Dieudonnée Togbe,Bernhard Ryffel
出处
期刊:ImmunoHorizons
[The American Association of Immunologists]
日期:2021-05-01
卷期号:5 (5): 273-283
标识
DOI:10.4049/immunohorizons.2000095
摘要
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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