title: Reduced Expression of HLA-DR on Monocytes During Severe Respiratory Syncytial Virus Infections.
abstract: BACKGROUND
  Respiratory syncytial virus (RSV) is a common cause of bronchiolitis in infants with a wide spectrum of disease severity. Besides environmental and genetic factors, it is thought that the innate immune system plays a pivotal role. The aim of this study was to investigate the expression of immune receptors on monocytes and the in vitro responsiveness from infants with severe RSV infections.
  
  
  METHODS
  Peripheral blood mononuclear cells (PBMCs) from infants with RSV infections were isolated. Classical, intermediate and nonclassical monocytes were immunophenotyped for the expression of CD14, CD16, human leukocyte antigen (HLA)-ABC and HLA-DR. PBMCs were stimulated with lipopolysaccharide to determine the secretion of tumor necrosis factor and interleukin (IL)-10 with enzyme-linked immunosorbent assay.
  
  
  RESULTS
  During RSV infection, intermediate monocytes are increased in the peripheral blood, whereas classical and nonclassical monocytes are reduced. The expression of CD14 and HLA-ABC is increased on monocytes, whereas the expression of HLA-DR is suppressed. Low HLA-DR expression is correlated with increased disease severity. PBMCs from infants with severe RSV infections show an impaired IL-10 response in vitro.
  
  
  CONCLUSIONS
  Phenotyping subpopulations of monocytes combined with in vitro responsiveness reveals significant differences between nonsevere and severe RSV infections. Reduced HLA-DR expression and impaired IL-10 production in vitro during severe RSV infections indicate that an imbalanced innate immune response may play an important role in disease severity.
authors.affiliation: From the Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Inge M L
authors.initials: IM
authors.lastname: Ahout
authors.forename: Jop
authors.initials: J
authors.lastname: Jans
authors.forename: Lilid
authors.initials: L
authors.lastname: Haroutiounian
authors.forename: Elles R
authors.initials: ER
authors.lastname: Simonetti
authors.forename: Christa
authors.initials: C
authors.lastname: van der Gaast-de Jongh
authors.forename: Dimitri A
authors.initials: DA
authors.lastname: Diavatopoulos
authors.forename: Marien I
authors.initials: MI
authors.lastname: de Jonge
authors.forename: Ronald
authors.initials: R
authors.lastname: de Groot
authors.forename: Gerben
authors.initials: G
authors.lastname: Ferwerda
mesh_terms: D015415:Biomarkers; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D016753:Interleukin-10 / Q000096:biosynthesis; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D010641:Phenotype; D018357:Respiratory Syncytial Virus Infections / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D006684:HLA-DR Antigens; D016753:Interleukin-10