Caspase-1-Independent Interleukin-1 beta Is Required for Clearance of Bordetella pertussis Infections and Whole-Cell Vaccine-Mediated Immunity: e107188

• Published in: PloS one Vol. 9; no. 9
• Main Authors: Place, David E, Muse, Sarah J, Kirimanjeswara, Girish S, Harvill, Eric T
• Format: Journal Article
• Language: English
• Published: 01.09.2014
• Subjects: Bordetella pertussis
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0107188

Whooping cough remains a significant disease worldwide and its re-emergence in highly vaccinated populations has been attributed to a combination of imperfect vaccines and evolution of the pathogen. The focus of this study was to examine the role of IL-1 alpha / beta and the inflammasome in generation of the interleukin-1 (IL-1) response, which is required for the clearance of Bordetella pertussis. We show that IL-1 beta but not IL-1 alpha is required for mediating the clearance of B. pertussis from the lungs of mice. We further found that IL-1 beta and IL-1R deficient mice, compared to wild-type, have similar but more persistent levels of inflammation, characterized by immune cell infiltration, with significantly increased IFN gamma and a normal IL-17A response during B. pertussis infection. Contrary to expectations, the cleavage of precursor IL-1 beta to its mature form did not require caspase-1 during primary infections within the lung despite being required by bone marrow-derived macrophages exposed to live bacteria. We also found that the caspase-1 inflammasome was not required for protective immunity against a B. pertussis challenge following vaccination with heat-killed whole cell B. pertussis, despite IL-1R signaling being required. These findings demonstrate that caspase-1-independent host factors are involved in the processing of protective IL-1 beta responses that are critical for bacterial clearance and vaccine-mediated immunity.