title: Innate Immune Responses after Airway Epithelial Stimulation with Mycobacterium bovis Bacille-Calmette Guérin.
abstract: Mycobacterium bovis bacilli Calmette-Guerin (BCG) is used as a benchmark to compare the immunogenicity of new vaccines against tuberculosis. This live vaccine is administered intradermal, but several new studies show that changing the route to mucosal immunisation represents an improved strategy. We analysed the immunomodulatory functions of BCG on human neutrophils and primary airway epithelial cells (AECs), as the early events of mucosal immune activation are unclear. Neutrophils and the primary epithelial cells were found to express the IL-17A receptor subunit IL-17RA, while the expression of IL-17RE was only observed on epithelial cells. BCG stimulation specifically reduced neutrophil IL-17RA and epithelial IL-17RE expression. BCG induced neutrophil extracellular traps (NETs), but did not have an effect on apoptosis as measured by transcription factor forkhead box O3 (FOXO3). BCG stimulation of AECs induced CXCL8 secretion and neutrophil endothelial passage towards infected epithelia. Infected epithelial cells and neutrophils were not found to be a source of IL-17 cytokines or the interstitial collagenase MMP-1. However, the addition of IFNγ or IL-17A to BCG stimulated primary epithelial cells increased epithelial IL-6 secretion, while the presence of IFNγ reduced neutrophil recruitment. Using our model of mucosal infection we revealed that BCG induces selective mucosal innate immune responses that could lead to induction of vaccine-mediated protection of the lung.
authors.affiliation: Department of Laboratory Medicine, Division of Microbiology, Immunology and Glycobiology, Lund University, Lund, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Tenland
authors.affiliation: Department of Laboratory Medicine, Division of Microbiology, Immunology and Glycobiology, Lund University, Lund, Sweden.
authors.forename: Gisela
authors.initials: G
authors.lastname: Håkansson
authors.affiliation: Department of Translational Medicine, Division of Clinical Microbiology, Lund University, Lund, Sweden.
authors.forename: Nader
authors.initials: N
authors.lastname: Alaridah
authors.affiliation: Department of Laboratory Medicine, Division of Microbiology, Immunology and Glycobiology, Lund University, Lund, Sweden.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Lutay
authors.affiliation: Department of Laboratory Medicine, Division of Microbiology, Immunology and Glycobiology, Lund University, Lund, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Rönnholm
authors.affiliation: Department of Clinical Sciences, Division of Respiratory Medicine and Allergology, Lund University, Lund, Sweden.
authors.forename: Oskar
authors.initials: O
authors.lastname: Hallgren
authors.affiliation: Department of Experimental Medical Science, Division of Lung Biology, Lund University, Lund, Sweden.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Westergren-Thorsson
authors.affiliation: Department of Translational Medicine, Division of Medical Microbiology, Lund University, Lund, Sweden.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Godaly
mesh_terms: D065206:Extracellular Traps / Q000276:immunology; D005260:Female; D000071316:Forkhead Box Protein O3 / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D009163:Mycobacterium bovis / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D053722:Receptors, Interleukin-17 / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology*
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; C573415:IFNG protein, human; C109985:IL17RA protein, human; C508600:IL6 protein, human; D020381:Interleukin-17; D015850:Interleukin-6; D053722:Receptors, Interleukin-17; D007371:Interferon-gamma