title: Respiratory syncytial virus infection of primary human mast cells induces the selective production of type I interferons, CXCL10, and CCL4.
abstract: BACKGROUND
  Respiratory syncytial virus (RSV) causes severe respiratory tract infections, which might have a role in the development of airway hyperreactivity. Mast cells are important effector cells in allergy, with sentinel cell roles in host defense. However, the role of mast cells in response to RSV infection is unknown.
  
  
  OBJECTIVE
  Human mast cell responses to RSV were investigated with a view to better understanding the role of mast cells in RSV-induced disease.
  
  
  METHODS
  Human cord blood-derived mast cells and the HMC-1 mast cell line were exposed to RSV or UV-inactivated RSV. Viral gene and protein expression were evaluated by using PCR and flow cytometry. The expression of interferon-stimulated genes and selected mediators were evaluated by using quantitative PCR and ELISA.
  
  
  RESULTS
  Human mast cells expressed multiple RSV genes after exposure to RSV, and a small percentage of mast cells supported RSV antigen protein expression. RSV induced mast cells to upregulate production of chemokines, including CCL4, CCL5, and CXCL10, as well as type I interferons, and interferon-stimulated gene expression. However, production of the granulocyte chemoattractants CXCL8 and CCL11 was not induced. Antibody blockade of the type I interferon receptor on human cord blood-derived mast cells reduced the RSV-mediated induction of CXCL10 and CCL4 but not CCL5. Leukotriene C4 production by mast cells was not enhanced by exposure to RSV.
  
  
  CONCLUSIONS
  Despite low levels of infection, human mast cells produce multiple chemokines in response to RSV through mechanisms that include responses to type I interferons. Such mast cell responses might enhance effector cell recruitment during RSV-induced disease.
authors.affiliation: Department of Microbiology and Immunology, Dalhousie Inflammation Group, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Ayham
authors.initials: A
authors.lastname: Al-Afif
authors.affiliation: Department of Microbiology and Immunology, Dalhousie Inflammation Group, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Pediatrics, Dalhousie Inflammation Group, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Raidan
authors.initials: R
authors.lastname: Alyazidi
authors.affiliation: Department of Microbiology and Immunology, Dalhousie Inflammation Group, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Oldford
authors.affiliation: Department of Microbiology and Immunology, Dalhousie Inflammation Group, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Pediatrics, Dalhousie Inflammation Group, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Yan Y
authors.initials: YY
authors.lastname: Huang
authors.affiliation: Department of Microbiology and Immunology, Dalhousie Inflammation Group, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Christine A
authors.initials: CA
authors.lastname: King
authors.affiliation: Canadian Center for Vaccinology, Izaak Walter Killam Health Centre, Halifax, Nova Scotia, Canada.
authors.forename: Nico
authors.initials: N
authors.lastname: Marr
authors.affiliation: Department of Microbiology and Immunology, Dalhousie Inflammation Group, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Haidl
authors.affiliation: Department of Microbiology and Immunology, Dalhousie Inflammation Group, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Pediatrics, Dalhousie Inflammation Group, Dalhousie University, Halifax, Nova Scotia, Canada; Canadian Center for Vaccinology, Izaak Walter Killam Health Centre, Halifax, Nova Scotia, Canada. Electronic address: robert.anderson@dal.ca.
authors.forename: Robert
authors.initials: R
authors.lastname: Anderson
authors.affiliation: Department of Microbiology and Immunology, Dalhousie Inflammation Group, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Pathology, Dalhousie Inflammation Group, Dalhousie University, Halifax, Nova Scotia, Canada. Electronic address: jean.marshall@dal.ca.
authors.forename: Jean S
authors.initials: JS
authors.lastname: Marshall
mesh_terms: D016535:Bronchial Hyperreactivity; D002460:Cell Line; D054407:Chemokine CCL4 / Q000378:metabolism*; D054357:Chemokine CXCL10 / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D008407:Mast Cells / Q000276:immunology* / Q000821:virology; D061251:Primary Cell Culture; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*
chemical_list: D054407:Chemokine CCL4; D054357:Chemokine CXCL10; D007370:Interferon Type I
keywords: Mast cells; chemokines; innate immunity; interferons; respiratory infection; respiratory syncytial virus; viral infection