Caspase-1-independent interleukin-1? is required for clearance of Bordetella pertussis infections and whole-cell vaccine-mediated immunity.

ABSTRACT: 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?/? 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? but not IL-1? is required for mediating the clearance of B. pertussis from the lungs of mice. We further found that IL-1? 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? and a normal IL-17A response during B. pertussis infection. Contrary to expectations, the cleavage of precursor IL-1? 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? responses that are critical for bacterial clearance and vaccine-mediated immunity.

SUBMITTER: Place DE 

PROVIDER: S-EPMC4157866 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature