title: Neutrophilic NLRP3 inflammasome-dependent IL-1β secretion regulates the γδT17 cell response in respiratory bacterial infections.
abstract: Traditionally regarded as simple foot soldiers of the innate immune response limited to the eradication of pathogens, neutrophils recently emerged as more complex cells endowed with a set of immunoregulatory functions. Using a model of invasive pneumococcal disease, we highlighted an unexpected key role for neutrophils as accessory cells in innate interleukin (IL)-17A production by lung resident Vγ6Vδ1+T cells via nucleotide-binding oligomerization domain receptor, pyrin-containing 3 (NLRP3) inflammasome-dependent IL-1β secretion. In vivo activation of the NLRP3 inflammasome in neutrophils required both host-derived and bacterial-derived signals. Elaborately, it relies on (i) alveolar macrophage-secreted TNF-α for priming and (ii) subsequent exposure to bacterial pneumolysin for activation. Interestingly, this mechanism can be translated to human neutrophils. Our work revealed the cellular and molecular dynamic events leading to γδT17 cell activation, and highlighted for the first time the existence of a fully functional NLRP3 inflammasome in lung neutrophils. This immune axis thus regulates the development of a protective host response to respiratory bacterial infections.
authors.affiliation: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, Lille, France.|Laboratoire Microbiologie Santé et Environnement, Ecole doctorale en Sciences et Technologies/ Faculté de Santé Publique, Université Libanaise, Tripoli, Liban.
authors.forename: M
authors.initials: M
authors.lastname: Hassane
authors.affiliation: Inflammation Research Center, VIB, Zwijnaarde, Belgium.|Department of Internal Medicine, Ghent University, Ghent, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Demon
authors.affiliation: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, Lille, France.
authors.forename: D
authors.initials: D
authors.lastname: Soulard
authors.affiliation: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, Lille, France.
authors.forename: J
authors.initials: J
authors.lastname: Fontaine
authors.affiliation: Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, Groningen, The Netherlands.
authors.forename: L E
authors.initials: LE
authors.lastname: Keller
authors.affiliation: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, Lille, France.
authors.forename: E C
authors.initials: EC
authors.lastname: Patin
authors.affiliation: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, Lille, France.
authors.forename: R
authors.initials: R
authors.lastname: Porte
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Prinz
authors.affiliation: CNRS, UMR7355, Experimental and Molecular Immunology and Neurogenetics, University, Orléans, France and IDM, University of Cape Town, RSA.
authors.forename: B
authors.initials: B
authors.lastname: Ryffel
authors.affiliation: Department of Clinical Infection, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
authors.forename: A
authors.initials: A
authors.lastname: Kadioglu
authors.affiliation: Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, Groningen, The Netherlands.
authors.forename: J-W
authors.initials: JW
authors.lastname: Veening
authors.affiliation: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, Lille, France.
authors.forename: J-C
authors.initials: JC
authors.lastname: Sirard
authors.affiliation: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Faveeuw
authors.affiliation: Inflammation Research Center, VIB, Zwijnaarde, Belgium.|Department of Internal Medicine, Ghent University, Ghent, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Lamkanfi
authors.affiliation: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, Lille, France.
authors.forename: F
authors.initials: F
authors.lastname: Trottein
authors.affiliation: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Paget
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology*; D011008:Pneumococcal Infections / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism; D012141:Respiratory Tract Infections / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013301:Streptolysins / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D058847:Inflammasomes; D020381:Interleukin-17; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013301:Streptolysins; D014409:Tumor Necrosis Factor-alpha; C032290:plY protein, Streptococcus pneumoniae