Bordetella pertussis-infected innate immune cells drive the anti-pertussis response of human airway epithelium

M M Kroes,A Miranda-Bedate,E Van Woudenbergh,E Pinelli,J De Wit,R H J Jacobi,G Den Hartog,J P M Van Putten

doi:10.1038/s41598-022-07603-8

M M Kroes, A Miranda-Bedate + Show 6 more

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https://doi.org/10.1038/s41598-022-07603-8

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Abstract

Pertussis is a severe respiratory tract infection caused by Bordetella pertussis. This bacterium infects the ciliated epithelium of the human airways. We investigated the epithelial cell response to B. pertussis infection in primary human airway epithelium (HAE) differentiated at air–liquid interface. Infection of the HAE cells mimicked several hallmarks of B. pertussis infection such as reduced epithelial barrier integrity and abrogation of mucociliary transport. Our data suggests mild immunological activation of HAE by B. pertussis indicated by secretion of IL-6 and CXCL8 and the enrichment of genes involved in bacterial recognition and innate immune processes. We identified IL-1β and IFNγ, present in conditioned media derived from B. pertussis-infected macrophage and NK cells, as essential immunological factors for inducing robust chemokine secretion by HAE in response to B. pertussis. In transwell migration assays, the chemokine-containing supernatants derived from this HAE induced monocyte migration. Our data suggests that the airway epithelium on its own has a limited immunological response to B. pertussis and that for a broad immune response communication with local innate immune cells is necessary. This highlights the importance of intercellular communication in the defense against B. pertussis infection and may assist in the rational design of improved pertussis vaccines.

Highlights

Pertussis is a severe respiratory tract infection caused by Bordetella pertussis
We investigate the immune response to B. pertussis at the human airway epithelium using primary human airway epithelial cells (HAE) differentiated at air–liquid interface
Fluorescent microscopy on the HAE cultures revealed the presence of several mucus producing ( Muc5AC+, Pink) and a large amount of ciliated (β-tubulin I V+, Green) cells which were connected by tight junctions (ZO-1+, Red) (Fig. 1B)

Summary

Introduction

Pertussis is a severe respiratory tract infection caused by Bordetella pertussis This bacterium infects the ciliated epithelium of the human airways. We identified IL-1β and IFNγ, present in conditioned media derived from B. pertussis-infected macrophage and NK cells, as essential immunological factors for inducing robust chemokine secretion by HAE in response to B. pertussis. Pertussis cases have been increasing in the last few decades despite high vaccination coverage, infecting an estimated 24.1 million individuals and causing 160,700 deaths in children younger than 5 years in 2 0142 Several reasons for this reemergence have been suggested including pathogen adaptation, waning of vaccine-induced immunity and suboptimal induction of a protective type of immune response by the acellular pertussis vaccine (aP)[3–5]. We show that the chemokines produced by these HAE effectively recruit monocytes

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