title: First-Breath-Induced Type 2 Pathways Shape the Lung Immune Environment.
abstract: From birth onward, the lungs are exposed to the external environment and therefore harbor a complex immunological milieu to protect this organ from damage and infection. We investigated the homeostatic role of the epithelium-derived alarmin interleukin-33 (IL-33) in newborn mice and discovered the immediate upregulation of IL-33 from the first day of life, closely followed by a wave of IL-13-producing type 2 innate lymphoid cells (ILC2s), which coincided with the appearance of alveolar macrophages (AMs) and their early polarization to an IL-13-dependent anti-inflammatory M2 phenotype. ILC2s contributed to lung quiescence in homeostasis by polarizing tissue resident AMs and induced an M2 phenotype in transplanted macrophage progenitors. ILC2s continued to maintain the M2 AM phenotype during adult life at the cost of a delayed response to Streptococcus pneumoniae infection in mice. These data highlight the homeostatic role of ILC2s in setting the activation threshold in the lung and underline their implications in anti-bacterial defenses.
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria; Department of Medicine I, Laboratory of Infection Biology, Medical University of Vienna, Vienna 1090, Austria; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Simona
authors.initials: S
authors.lastname: Saluzzo
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria; Department of Medicine I, Laboratory of Infection Biology, Medical University of Vienna, Vienna 1090, Austria.
authors.forename: Anna-Dorothea
authors.initials: AD
authors.lastname: Gorki
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Batika M J
authors.initials: BMJ
authors.lastname: Rana
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria; Department of Medicine I, Laboratory of Infection Biology, Medical University of Vienna, Vienna 1090, Austria.
authors.forename: Rui
authors.initials: R
authors.lastname: Martins
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Seth
authors.initials: S
authors.lastname: Scanlon
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria; Department of Medicine I, Laboratory of Infection Biology, Medical University of Vienna, Vienna 1090, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Starkl
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria; Department of Medicine I, Laboratory of Infection Biology, Medical University of Vienna, Vienna 1090, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Lakovits
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria; Department of Medicine I, Laboratory of Infection Biology, Medical University of Vienna, Vienna 1090, Austria.
authors.forename: Anastasiya
authors.initials: A
authors.lastname: Hladik
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria; Department of Medicine I, Laboratory of Infection Biology, Medical University of Vienna, Vienna 1090, Austria.
authors.forename: Ana
authors.initials: A
authors.lastname: Korosec
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria; Department of Medicine I, Laboratory of Infection Biology, Medical University of Vienna, Vienna 1090, Austria.
authors.forename: Omar
authors.initials: O
authors.lastname: Sharif
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria; Department of Medicine I, Laboratory of Infection Biology, Medical University of Vienna, Vienna 1090, Austria.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Warszawska
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Jolin
authors.affiliation: Institute of Pathology Überlingen, Überlingen 88662, Germany.
authors.forename: Ildiko
authors.initials: I
authors.lastname: Mesteri
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. Electronic address: anm@mrc-lmb.cam.ac.uk.
authors.forename: Andrew N J
authors.initials: ANJ
authors.lastname: McKenzie
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria; Department of Medicine I, Laboratory of Infection Biology, Medical University of Vienna, Vienna 1090, Austria. Electronic address: sylvia.knapp@meduniwien.ac.at.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Knapp
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D018793:Interleukin-13 / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011008:Pneumococcal Infections / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D018793:Interleukin-13
keywords: S. pneumoniae; alarmin; alveolar macrophage; first breath; immune homeostasis; lung; newborn; pneumoniae