title: Molecular signatures of the evolving immune response in mice following a Bordetella pertussis infection.
abstract: Worldwide resurgence of pertussis necessitates the need for improvement of pertussis vaccines and vaccination strategies. Since natural infections induce a longer-lasting immunity than vaccinations, detailed knowledge of the immune responses following natural infection can provide important clues for such improvement. The purpose was to elucidate the kinetics of the protective immune response evolving after experimental Bordetella pertussis (B. pertussis) infection in mice. Data were collected from (i) individual analyses, i.e. microarray, flow cytometry, multiplex immunoassays, and bacterial clearance; (ii) twelve time points during the infection; and (iii) different tissues involved in the immune responses, i.e. lungs, spleen and blood. Combined data revealed detailed insight in molecular and cellular sequence of events connecting different phases (innate, bridging and adaptive) of the immune response following the infection. We detected a prolonged acute phase response, broad pathogen recognition, and early gene signatures of subsequent T-cell recruitment in the lungs. Activation of particular transcription factors and specific cell markers provided insight into the time course of the transition from innate towards adaptive immune responses, which resulted in a broad spectrum of systemic antibody subclasses and splenic Th1/Th17 memory cells against B. pertussis. In addition, signatures preceding the local generation of Th1 and Th17 cells as well as IgA in the lungs, considered key elements in protection against B. pertussis, were established. In conclusion, molecular and cellular immunological processes in response to live B. pertussis infection were unraveled, which may provide guidance in selecting new vaccine candidates that should evoke local and prolonged protective immune responses.
authors.affiliation: Intravacc, Bilthoven, The Netherlands; Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden, The Netherlands.
authors.forename: René H M
authors.initials: RH
authors.lastname: Raeven
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Jolanda
authors.initials: J
authors.lastname: Brummelman
authors.affiliation: Centre for Health Protection (GZB), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Jeroen L A
authors.initials: JL
authors.lastname: Pennings
authors.affiliation: Intravacc, Bilthoven, The Netherlands.
authors.forename: Olaf E M
authors.initials: OE
authors.lastname: Nijst
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Betsy
authors.initials: B
authors.lastname: Kuipers
authors.affiliation: Intravacc, Bilthoven, The Netherlands.
authors.forename: Laura E R
authors.initials: LE
authors.lastname: Blok
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Kina
authors.initials: K
authors.lastname: Helm
authors.affiliation: Intravacc, Bilthoven, The Netherlands.
authors.forename: Elly
authors.initials: E
authors.lastname: van Riet
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Jiskoot
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Cecile A C M
authors.initials: CA
authors.lastname: van Els
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Wanda G H
authors.initials: WG
authors.lastname: Han
authors.affiliation: Intravacc, Bilthoven, The Netherlands; Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden, The Netherlands.
authors.forename: Gideon F A
authors.initials: GF
authors.lastname: Kersten
authors.affiliation: Intravacc, Bilthoven, The Netherlands.
authors.forename: Bernard
authors.initials: B
authors.lastname: Metz
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D001885:Bordetella Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D001886:Bordetella pertussis / Q000276:immunology; D003167:Complement Activation; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D007113:Immunity, Innate; D007070:Immunoglobulin A / Q000096:biosynthesis; D007156:Immunologic Memory; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology; D023084:alpha-Defensins / Q000235:genetics / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines; D007070:Immunoglobulin A; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D023084:alpha-Defensins