Naturally circulating pertactin-deficient Bordetella pertussis strains induce distinct gene expression and inflammatory signatures in human dendritic cells
Kroes, Michiel M; Miranda-Bedate, Alberto; Hovingh, Elise S; Jacobi, Ronald; Schot, Corrie; Pupo, Elder; Raeven, René H M; van der Ark, Arno A J; van Putten, Jos P M; de Wit, Jelle; Mariman, Rob; Pinelli, Elena
(2021) Emerging Microbes and Infections, volume 10, issue 1, pp. 1358 - 1368
(Article)
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
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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.
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Keywords: Pathogen adaptation, RNAseq, dendritic cell, human, innate immunity, pertactin, proteomics, transcriptomics, Parasitology, Epidemiology, Microbiology, Immunology, Drug Discovery, Virology, Infectious Diseases
ISSN: 2222-1751
Publisher: Nature Publishing Group
Note: Funding Information: This work was supported by the Dutch Ministry of Health, grant V/150407/21/AD. Publisher Copyright: © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd.
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