title: Meta-Analysis of Pulmonary Transcriptomes from Differently Primed Mice Identifies Molecular Signatures to Differentiate Immune Responses followingBordetella pertussisChallenge.
abstract: Respiratory infection withBordetella pertussisleads to severe effects in the lungs. The resulting immunity and also immunization with pertussis vaccines protect against disease, but the induced type of immunity and longevity of the response are distinct. In this study the effects of priming, by either vaccination or infection, on a subsequent pathogen encounter were studied. To that end, three postchallenge transcriptome datasets of previously primed mice were combined and compared to the responses in unprimed control mice. In total, 205 genes showed different transcription activity. A coexpression network analysis assembled these genes into 27 clusters, combined into six groups with overlapping biological function. Local pulmonary immunity was only present in mice with infection-induced immunity. Complement-mediated responses were more prominent in mice immunized with an outer membrane vesicle pertussis vaccine than in mice that received a whole-cell pertussis vaccine. Additionally, 46 genes encoding for secreted proteins may serve as markers in blood for the degree of protection (Cxcl9, Gp2,andPla2g2d), intensity of infection (Retnla, Saa3, Il6,andIl1b), or adaptive recall responses (Ighg, C1qb). The molecular signatures elucidated in this study contribute to better understanding of functional interactions in challenge-induced responses in relation to pertussis immunity.
authors.affiliation: Institute for Translational Vaccinology (Intravacc), Bilthoven, Netherlands; Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden, Netherlands.
authors.forename: René H M
authors.identifier: 0000-0002-1063-271X
authors.initials: RH
authors.lastname: Raeven
authors.affiliation: Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, Netherlands.
authors.forename: Jeroen L A
authors.identifier: 0000-0002-9188-6358
authors.initials: JL
authors.lastname: Pennings
authors.affiliation: Institute for Translational Vaccinology (Intravacc), Bilthoven, Netherlands.
authors.forename: Elly
authors.initials: E
authors.lastname: van Riet
authors.affiliation: Institute for Translational Vaccinology (Intravacc), Bilthoven, Netherlands; Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden, Netherlands.
authors.forename: Gideon F A
authors.initials: GF
authors.lastname: Kersten
authors.affiliation: Institute for Translational Vaccinology (Intravacc), Bilthoven, Netherlands.
authors.forename: Bernard
authors.initials: B
authors.lastname: Metz
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D001886:Bordetella pertussis / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D007111:Immunity, Cellular / Q000235:genetics*; D007156:Immunologic Memory / Q000235:genetics; D008168:Lung / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010567:Pertussis Vaccine / Q000008:administration & dosage / Q000276:immunology*; D059467:Transcriptome; D014611:Vaccination; D014917:Whooping Cough / Q000235:genetics / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D015415:Biomarkers; D010567:Pertussis Vaccine