title: Antibodies enhance CXCL10 production during RSV infection of infant and adult immune cells.
abstract: Respiratory syncytial virus (RSV) bronchiolitis is a major burden in infants below three months of age, when the primary immune response is mainly dependent on innate immunity and maternal antibodies. We investigated the influence of antibodies on innate immunity during RSV infection. PBMCs from infants and adults were stimulated with live RSV and inactivated RSV in combination with antibody-containing and antibody-depleted serum. The immune response was determined by transcriptome analysis and chemokine levels were measured using ELISA and flow cytometry. Microarray data showed that CXCL10 gene transcription was RSV dependent, whereas CXCL11 and IFNα were upregulated in an antibody-dependent manner. Although the presence of antibodies reduces RSV infection rate, it enhances the innate immune response. In adult immune cells, antibodies enhance CXCL10, CXCL11, IFNα and IFNγ production in response to RSV infection. Contrary, in infant immune cells only CXCL10 was enhanced in an antibody-dependent manner. Monocytes are the main source of CXCL10 and they produce CXCL10 in both an antibody- and virus-dependent manner. This study shows that antibodies enhance CXCL10 production in infant immune cells. CXCL10 has been implicated in exuberating the inflammatory response during viral infections and antibodies could therefore play a role in the pathogenesis of RSV infections.
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Marloes
authors.initials: M
authors.lastname: Vissers
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Inge
authors.initials: I
authors.lastname: Schreurs
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jop
authors.initials: J
authors.lastname: Jans
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jacco
authors.initials: J
authors.lastname: Heldens
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: de Groot
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Marien I
authors.initials: MI
authors.lastname: de Jonge
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Gerben.Ferwerda@radboudumc.nl.
authors.forename: Gerben
authors.initials: G
authors.lastname: Ferwerda
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology*; D054357:Chemokine CXCL10 / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D014158:Transcription, Genetic
chemical_list: D000906:Antibodies; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D016207:Cytokines
keywords: Antibodies; CXCL10; Infants; Innate immunity; RSV