title: Caspase-1-independent interleukin-1β 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-1α/β 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-1β but not IL-1α is required for mediating the clearance of B. pertussis from the lungs of mice. We further found that IL-1β 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 IFNγ and a normal IL-17A response during B. pertussis infection. Contrary to expectations, the cleavage of precursor IL-1β 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-1β responses that are critical for bacterial clearance and vaccine-mediated immunity.
authors.affiliation: Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania, United States of America; Graduate Program in Immunology and Infectious Diseases, Pennsylvania State University, University Park, Pennsylvania, United States of America.
authors.forename: David E
authors.initials: DE
authors.lastname: Place
authors.affiliation: Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania, United States of America; Graduate Program in Biochemistry, Microbiology and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania, United States of America.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Muse
authors.affiliation: Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania, United States of America.
authors.forename: Girish S
authors.initials: GS
authors.lastname: Kirimanjeswara
authors.affiliation: Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania, United States of America.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Harvill
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001885:Bordetella Infections / Q000276:immunology* / Q000473:pathology; D001886:Bordetella pertussis / Q000276:immunology / Q000502:physiology*; D020170:Caspase 1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D051379:Mice; D010567:Pertussis Vaccine / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D053583:Interleukin-1beta; D010567:Pertussis Vaccine; D020170:Caspase 1