Reduced Expression of HLA-DR on Monocytes During Severe Respiratory Syncytial Virus Infections

Pediatr Infect Dis J. 2016 Mar;35(3):e89-96. doi: 10.1097/INF.0000000000001007.

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.

MeSH terms

  • Biomarkers
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Gene Expression*
  • HLA-DR Antigens / genetics*
  • HLA-DR Antigens / immunology*
  • Humans
  • Immunophenotyping
  • Infant
  • Interleukin-10 / biosynthesis
  • Leukocyte Count
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Monocytes / immunology*
  • Monocytes / metabolism*
  • Phenotype
  • Respiratory Syncytial Virus Infections / diagnosis
  • Respiratory Syncytial Virus Infections / genetics*
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Virus, Human / immunology*
  • Risk Factors
  • Severity of Illness Index

Substances

  • Biomarkers
  • HLA-DR Antigens
  • Interleukin-10