Abstract

Respiratory infections caused by Bordetella pertussis are reemerging despite high pertussis vaccination coverage. Since the introduction of the acellular pertussis vaccine in the late twentieth century, circulating B. pertussis strains increasingly lack expression of the vaccine component pertactin (Prn). In some countries, up to 90% of the circulating B. pertussis strains are deficient in Prn. To better understand the resurgence of pertussis, we investigated the response of human monocyte-derived dendritic cells (moDCs) to naturally circulating Prn-expressing (Prn-Pos) and Prn-deficient (Prn-Neg) B. pertussis strains from 2016 in the Netherlands. Transcriptome analysis of moDC showed enriched IFNα response-associated gene expression after exposure to Prn-Pos B. pertussis strains, whereas the Prn-Neg strains induced enriched expression of interleukin- and TNF-signaling genes, as well as other genes involved in immune activation. Multiplex immune assays confirmed enhanced proinflammatory cytokine secretion by Prn-Neg stimulated moDC. Comparison of the proteomes from the Prn-Pos and Prn-Neg strains revealed, next to the difference in Prn, differential expression of a number of other proteins including several proteins involved in metabolic processes. Our findings indicate that Prn-deficient B. pertussis strains induce a distinct and stronger immune activation of moDCs than the Prn-Pos strains. These findings highlight the role of pathogen adaptation in the resurgence of pertussis as well as the effects that vaccine pressure can have on a bacterial population.

Details

Title
Naturally circulating pertactin-deficient Bordetella pertussis strains induce distinct gene expression and inflammatory signatures in human dendritic cells
Author
Kroes, Michiel M 1 ; Miranda-Bedate, Alberto 2   VIAFID ORCID Logo  ; Hovingh, Elise S 2 ; Jacobi, Ronald 2 ; Schot, Corrie 2 ; Elder Pupo 3 ; Raeven, René H M 3 ; Arno A J van der Ark 3 ; Jos P M van Putten 4   VIAFID ORCID Logo  ; de Wit, Jelle 2 ; Mariman, Rob 2   VIAFID ORCID Logo  ; Pinelli, Elena 2   VIAFID ORCID Logo 

 Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, Netherlands; Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands 
 Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, Netherlands 
 Institute for Translational Vaccinology (Intravacc), Bilthoven, Netherlands 
 Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands 
Pages
1358-1368
Publication year
2021
Publication date
Dec 2021
Publisher
Taylor & Francis Ltd.
e-ISSN
22221751
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3190428794
Copyright
© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.