Respiratory Syncytial Virus Infects Regulatory B Cells in Human Neonates via Chemokine Receptor CX3CR1 and Promotes Lung Disease Severity

Dania Zhivaki; Sébastien Lemoine; Annick Lim; Ahsen Morva; Pierre-Olivier Vidalain; Liliane Schandene; Nicoletta Casartelli; Marie-Anne Rameix-Welti; Pierre-Louis Hervé; Edith Dériaud; Benoit Beitz; Maryline Ripaux-Lefevre; Jordi Miatello; Brigitte Lemercier; Valerie Lorin; Delphyne Descamps; Jenna Fix; Jean-François Eléouët; Sabine Riffault; Olivier Schwartz; Fabrice Porcheray; Françoise Mascart; Hugo Mouquet; Xiaoming Zhang; Pierre Tissières; Richard Lo-Man

doi:10.1016/j.immuni.2017.01.010

Respiratory Syncytial Virus Infects Regulatory B Cells in Human Neonates via Chemokine Receptor CX3CR1 and Promotes Lung Disease Severity

Immunity. 2017 Feb 21;46(2):301-314. doi: 10.1016/j.immuni.2017.01.010.

Authors

Dania Zhivaki¹, Sébastien Lemoine², Annick Lim³, Ahsen Morva⁴, Pierre-Olivier Vidalain⁵, Liliane Schandene⁶, Nicoletta Casartelli⁷, Marie-Anne Rameix-Welti⁸, Pierre-Louis Hervé⁹, Edith Dériaud², Benoit Beitz¹⁰, Maryline Ripaux-Lefevre¹⁰, Jordi Miatello¹¹, Brigitte Lemercier³, Valerie Lorin¹², Delphyne Descamps⁹, Jenna Fix⁹, Jean-François Eléouët⁹, Sabine Riffault⁹, Olivier Schwartz⁷, Fabrice Porcheray¹⁰, Françoise Mascart¹³, Hugo Mouquet¹², Xiaoming Zhang¹⁴, Pierre Tissières¹¹, Richard Lo-Man¹⁵

Affiliations

¹ Neonatal Immunity Group, Human Histopathology and Animal Models, Institut Pasteur, Paris 75724, France; Paris 7 Diderot University, Paris 75724, France.
² Régulation Immunitaire et Vaccinologie, Institut Pasteur, Paris 75724, France; INSERM U1041, Paris 75724, France.
³ Departement d'Immunologie, Institut Pasteur, Paris 75724, France.
⁴ Neonatal Immunity Group, Human Histopathology and Animal Models, Institut Pasteur, Paris 75724, France.
⁵ Unité de Génomique virale et vaccination, Institut Pasteur, Paris 75724, France.
⁶ Immunobiology Clinic, Hopital Erasme, Brussels 1070, Belgium.
⁷ Virus et Immunité, Institut Pasteur, Paris 75724, France; UMR CNRS 3568, Paris 75724, France.
⁸ INSERM U1173, Versailles-Saint-Quentin University, Saint-Quentin en Yvelines 78180, France; AP-HP, Laboratoire de Microbiologie, Hôpital Ambroise Paré, Boulogne-Billancourt 92100, France.
⁹ Unité de Virologie et Immunologie Moléculaires, INRA, Université Paris-Saclay, Jouy-en-Josas 78350, France.
¹⁰ Bioaster Microbiology Technology Institute, Paris 75015, France.
¹¹ 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.
¹² Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris 75724, France; INSERM U1222, Paris 75724, France.
¹³ Immunobiology Clinic, Hopital Erasme, Brussels 1070, Belgium; Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles, Brussels 1070, Belgium.
¹⁴ 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.
¹⁵ Neonatal Immunity Group, Human Histopathology and Animal Models, Institut Pasteur, Paris 75724, France. Electronic address: [email protected].

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.

Keywords: Breg cell; bronchiolitis; newborn; respiratory syncytial virus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

B-Lymphocytes, Regulatory / immunology*
B-Lymphocytes, Regulatory / virology
Bronchiolitis, Viral / immunology*
Bronchiolitis, Viral / pathology
CD4-Positive T-Lymphocytes / immunology
CX3C Chemokine Receptor 1
Enzyme-Linked Immunosorbent Assay
Enzyme-Linked Immunospot Assay
Gene Expression Profiling
Humans
Infant, Newborn
Lymphocyte Activation / immunology
Oligonucleotide Array Sequence Analysis
Receptors, Chemokine / immunology*
Respiratory Syncytial Virus Infections / immunology*
Respiratory Syncytial Virus Infections / pathology
Respiratory Syncytial Viruses
Transcriptome

Substances

CX3C Chemokine Receptor 1
CX3CR1 protein, human
Receptors, Chemokine