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- Title
Bordetella pertussis Induces Interferon Gamma Production by Natural Killer Cells, Resulting in Chemoattraction by Respiratory Epithelial Cells.
- Authors
Hartog, Gerco den; Schijf, Marcel A; Berbers, Guy A M; Klis, Fiona R M van der; Buisman, Anne-Marie; den Hartog, Gerco; van der Klis, Fiona R M
- Abstract
<bold>Background: </bold>Whooping cough is caused by infection of the airways with Bordetella pertussis (Bp). As interferon gamma (IFN-γ) is essential for protective immunity against Bp, we investigated how IFN-γ is induced by Bp or the virulence antigens filamentous hemagglutinin adhesin, pertactin, or pertussis toxin, and how IFN-γ contributes to local immune responses in humans.<bold>Methods: </bold>Peripheral blood mononuclear cells (PBMCs) from healthy donors and/or respiratory epithelial cells were stimulated with soluble antigens or inactivated intact Bp and the presence or absence of blocking antibodies or chemokines. Supernatants and cells were analyzed for IFN-γ and chemokine production, and lymphocyte migration was tested using epithelial supernatants.<bold>Results: </bold>The soluble antigens failed to induce IFN-γ production, whereas inactivated Bp induced IFN-γ production. Natural killer (NK) cells were the main source of IFN-γ production, which was enhanced by interleukin 15. Epithelial-PBMC co-cultures showed robust IFN-γ-dependent CXCL9 and CXCL10 production by the epithelial cells following stimulation with IFN-γ and Bp. The epithelial-derived chemokines resulted in CXCR3-dependent recruitment of NK and T cells.<bold>Conclusions: </bold>Inactivated Bp, but not antigens, induced potent IFN-γ production by NK cells, resulting in chemoattraction of lymphocytes toward the respiratory epithelium. These data provide insight into the requirements for IFN-γ production and how IFN-γ enhances local immune responses to prevent Bp-mediated disease.
- Subjects
MONONUCLEAR leukocytes; KILLER cells; BORDETELLA pertussis; INTERFERONS; EPITHELIAL cells; CHEMOKINES
- Publication
Journal of Infectious Diseases, 2022, Vol 225, Issue 7, p1248
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiaa140