title: Immunological Signatures after Bordetella pertussis Infection Demonstrate Importance of Pulmonary Innate Immune Cells.
abstract: Effective immunity against Bordetella pertussis is currently under discussion following the stacking evidence of pertussis resurgence in the vaccinated population. Natural immunity is more effective than vaccine-induced immunity indicating that knowledge on infection-induced responses may contribute to improve vaccination strategies. We applied a systems biology approach comprising microarray, flow cytometry and multiplex immunoassays to unravel the molecular and cellular signatures in unprotected mice and protected mice with infection-induced immunity, around a B. pertussis challenge. Pre-existing systemic memory Th1/Th17 cells, memory B-cells, and mucosal IgA specific for Ptx, Vag8, Fim2/3 were detected in the protected mice 56 days after an experimental infection. In addition, pre-existing high activity and reactivation of pulmonary innate cells such as alveolar macrophages, M-cells and goblet cells was detected. The pro-inflammatory responses in the lungs and serum, and neutrophil recruitment in the spleen upon an infectious challenge of unprotected mice were absent in protected mice. Instead, fast pulmonary immune responses in protected mice led to efficient bacterial clearance and harbored potential new gene markers that contribute to immunity against B. pertussis. These responses comprised of innate makers, such as Clca3, Retlna, Glycam1, Gp2, and Umod, next to adaptive markers, such as CCR6+ B-cells, CCR6+ Th17 cells and CXCR6+ T-cells as demonstrated by transcriptome analysis. In conclusion, besides effective Th1/Th17 and mucosal IgA responses, the primary infection-induced immunity benefits from activation of pulmonary resident innate immune cells, achieved by local pathogen-recognition. These molecular signatures of primary infection-induced immunity provided potential markers to improve vaccine-induced immunity against B. pertussis.
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.identifier: http://orcid.org/0000-0002-1063-271X
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: Intravacc, Bilthoven, The Netherlands.
authors.forename: Larissa
authors.initials: L
authors.lastname: van der Maas
authors.affiliation: Intravacc, Bilthoven, The Netherlands.
authors.forename: Wichard
authors.initials: W
authors.lastname: Tilstra
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: 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: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Cécile A C M
authors.initials: CA
authors.lastname: van Els
authors.affiliation: Intravacc, Bilthoven, The Netherlands.
authors.forename: Elly
authors.initials: E
authors.lastname: van Riet
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: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000378:metabolism; D001886:Bordetella pertussis / Q000276:immunology / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D007113:Immunity, Innate; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D013154:Spleen / Q000276:immunology; D014917:Whooping Cough / Q000097:blood / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines