Bordetella pertussis induces IFN-γ production by NK cells resulting in chemo-attraction by respiratory epithelial cells

• Published in: The Journal of infectious diseases
• Main Authors: den Hartog, Gerco, Schijf, Marcel A, Berbers, Guy A M, van der Klis, Fiona R M, Buisman, Anne-Marie
• Format: Journal Article
• Language: English
• Published: United States 27-03-2020
• Subjects: CXCL10; whooping cough; IFN-γ; CXCR3; cell migration; B. pertussis; NK; respiratory epithelium
• ISSN: 1537-6613

Whooping cough is caused by infection of the airways with Bordetella pertussis (Bp). As IFN-γ is essential for protective immunity against Bp we investigated how IFN-γ is induced by Bp or the virulence antigens FHA, Prn or PT, and how IFN-γ contributes to local immune responses in humans.
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 tested using epithelial supernatants.
The soluble antigens failed to induce IFN-γ production, whereas inactivated Bp induced IFN-γ production. NK cells were the main source of IFN-γ production, which was enhanced by IL-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.
Inactivated Bp, but not antigens, induced potent IFN-γ production by NK cells, resulting in chemo-attraction of lymphocytes towards 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.