title: Respiratory Syncytial Virus Infects Regulatory B Cells in Human Neonates via Chemokine Receptor CX3CR1 and Promotes Lung Disease Severity.
abstract: Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in infants and is characterized by pulmonary infiltration of B cells in fatal cases. We analyzed the B cell compartment in human newborns and identified a population of neonatal regulatory B lymphocytes (nBreg cells) that produced interleukin 10 (IL-10) in response to RSV infection. The polyreactive B cell receptor of nBreg cells interacted with RSV protein F and induced upregulation of chemokine receptor CX3CR1. CX3CR1 interacted with RSV glycoprotein G, leading to nBreg cell infection and IL-10 production that dampened T helper 1 (Th1) cytokine production. In the respiratory tract of neonates with severe RSV-induced acute bronchiolitis, RSV-infected nBreg cell frequencies correlated with increased viral load and decreased blood memory Th1 cell frequencies. Thus, the frequency of nBreg cells is predictive of the severity of acute bronchiolitis disease and nBreg cell activity may constitute an early-life host response that favors microbial pathogenesis.
authors.affiliation: Neonatal Immunity Group, Human Histopathology and Animal Models, Institut Pasteur, Paris 75724, France; Paris 7 Diderot University, Paris 75724, France.
authors.forename: Dania
authors.initials: D
authors.lastname: Zhivaki
authors.affiliation: Régulation Immunitaire et Vaccinologie, Institut Pasteur, Paris 75724, France; INSERM U1041, Paris 75724, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lemoine
authors.affiliation: Departement d'Immunologie, Institut Pasteur, Paris 75724, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Lim
authors.affiliation: Neonatal Immunity Group, Human Histopathology and Animal Models, Institut Pasteur, Paris 75724, France.
authors.forename: Ahsen
authors.initials: A
authors.lastname: Morva
authors.affiliation: Unité de Génomique virale et vaccination, Institut Pasteur, Paris 75724, France.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Vidalain
authors.affiliation: Immunobiology Clinic, Hopital Erasme, Brussels 1070, Belgium.
authors.forename: Liliane
authors.initials: L
authors.lastname: Schandene
authors.affiliation: Virus et Immunité, Institut Pasteur, Paris 75724, France; UMR CNRS 3568, Paris 75724, France.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Casartelli
authors.affiliation: INSERM U1173, Versailles-Saint-Quentin University, Saint-Quentin en Yvelines 78180, France; AP-HP, Laboratoire de Microbiologie, Hôpital Ambroise Paré, Boulogne-Billancourt 92100, France.
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Rameix-Welti
authors.affiliation: Unité de Virologie et Immunologie Moléculaires, INRA, Université Paris-Saclay, Jouy-en-Josas 78350, France.
authors.forename: Pierre-Louis
authors.initials: PL
authors.lastname: Hervé
authors.affiliation: Régulation Immunitaire et Vaccinologie, Institut Pasteur, Paris 75724, France; INSERM U1041, Paris 75724, France.
authors.forename: Edith
authors.initials: E
authors.lastname: Dériaud
authors.affiliation: Bioaster Microbiology Technology Institute, Paris 75015, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Beitz
authors.affiliation: Bioaster Microbiology Technology Institute, Paris 75015, France.
authors.forename: Maryline
authors.initials: M
authors.lastname: Ripaux-Lefevre
authors.affiliation: APHP, Pediatric ICU and Neonatal Medicine, Paris South University Hospitals, Le Kremlin-Bicetre 94270, France; School of Medicine, Paris South University, Le Kremlin-Bicêtre 94270, France; Institute of Integrative Biology of the Cell - UMR 9196, Paris Saclay University, Gif-sur-Yvette 91190, France.
authors.forename: Jordi
authors.initials: J
authors.lastname: Miatello
authors.affiliation: Departement d'Immunologie, Institut Pasteur, Paris 75724, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Lemercier
authors.affiliation: Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris 75724, France; INSERM U1222, Paris 75724, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Lorin
authors.affiliation: Unité de Virologie et Immunologie Moléculaires, INRA, Université Paris-Saclay, Jouy-en-Josas 78350, France.
authors.forename: Delphyne
authors.initials: D
authors.lastname: Descamps
authors.affiliation: Unité de Virologie et Immunologie Moléculaires, INRA, Université Paris-Saclay, Jouy-en-Josas 78350, France.
authors.forename: Jenna
authors.initials: J
authors.lastname: Fix
authors.affiliation: Unité de Virologie et Immunologie Moléculaires, INRA, Université Paris-Saclay, Jouy-en-Josas 78350, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Eléouët
authors.affiliation: Unité de Virologie et Immunologie Moléculaires, INRA, Université Paris-Saclay, Jouy-en-Josas 78350, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Riffault
authors.affiliation: Virus et Immunité, Institut Pasteur, Paris 75724, France; UMR CNRS 3568, Paris 75724, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Schwartz
authors.affiliation: Bioaster Microbiology Technology Institute, Paris 75015, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Porcheray
authors.affiliation: Immunobiology Clinic, Hopital Erasme, Brussels 1070, Belgium; Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles, Brussels 1070, Belgium.
authors.forename: Françoise
authors.initials: F
authors.lastname: Mascart
authors.affiliation: Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris 75724, France; INSERM U1222, Paris 75724, France.
authors.forename: Hugo
authors.initials: H
authors.lastname: Mouquet
authors.affiliation: Unit of Innate Defense and Immune Modulation, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhang
authors.affiliation: APHP, Pediatric ICU and Neonatal Medicine, Paris South University Hospitals, Le Kremlin-Bicetre 94270, France; School of Medicine, Paris South University, Le Kremlin-Bicêtre 94270, France; Institute of Integrative Biology of the Cell - UMR 9196, Paris Saclay University, Gif-sur-Yvette 91190, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Tissières
authors.affiliation: Neonatal Immunity Group, Human Histopathology and Animal Models, Institut Pasteur, Paris 75724, France. Electronic address: richard.lo-man@pasteur.fr.
authors.forename: Richard
authors.initials: R
authors.lastname: Lo-Man
mesh_terms: D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000821:virology; D001990:Bronchiolitis, Viral / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D000073883:CX3C Chemokine Receptor 1; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D020869:Gene Expression Profiling; D006801:Humans; D007231:Infant, Newborn; D008213:Lymphocyte Activation / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D019707:Receptors, Chemokine / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology; D012136:Respiratory Syncytial Viruses; D059467:Transcriptome
chemical_list: D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D019707:Receptors, Chemokine
keywords: Breg cell; bronchiolitis; newborn; respiratory syncytial virus