Naturally circulating pertactin-deficient Bordetella pertussis strains induce distinct gene expression and inflammatory signatures in human dendritic cells
Autor: | 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, LS Equine Muscoskeletal Biology, Infectiebiologie, dI&I I&I-2 |
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Přispěvatelé: | LS Equine Muscoskeletal Biology, Infectiebiologie, dI&I I&I-2 |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Bordetella pertussis dendritic cell Whooping Cough Epidemiology 030106 microbiology Immunology Adaptation Biological Microbiology pertactin Proinflammatory cytokine transcriptomics 03 medical and health sciences proteomics Immune system Virology Drug Discovery Humans Secretion human Virulence Factors Bordetella innate immunity Inflammation Pertussis Vaccine Innate immune system biology Gene Expression Profiling Interleukin Dendritic Cells General Medicine Dendritic cell RNAseq biology.organism_classification Toll-Like Receptor 2 Toll-Like Receptor 4 Pathogen adaptation 030104 developmental biology Infectious Diseases Host-Pathogen Interactions Cytokines Parasitology Pertactin Transcriptome Research Article Bacterial Outer Membrane Proteins |
Zdroj: | Emerging Microbes & Infections article-version (VoR) Version of Record Emerging Microbes and Infections, 10(1), 1358. Nature Publishing Group |
ISSN: | 2222-1751 |
DOI: | 10.6084/m9.figshare.14790474 |
Popis: | 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. |
Databáze: | OpenAIRE |
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