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

Ahout, Inge M. L. MD; Jans, Jop MD; Haroutiounian, Lilid MD; Simonetti, Elles R. BSc; van der Gaast-de Jongh, Christa BSc; Diavatopoulos, Dimitri A. PhD; de Jonge, Marien I. PhD; de Groot, Ronald MD, PhD; Ferwerda, Gerben MD, PhD

The Pediatric Infectious Disease Journal: March 2016 - Volume 35 - Issue 3 - p e89–e96
doi: 10.1097/INF.0000000000001007
Pathogenesis and Host Response

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.

Supplemental Digital Content is available in the text.

From the Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.

Accepted for publication October 18, 2015.

I.M.L.A. and J.J. contributed equally to this work.

I.M.L.A. and G.F. were supported by the Virgo consortium, funded by the Dutch government project number FES0908, and by the Netherlands Genomics Initiative (NGI) project number 050-060-452. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

The authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

Address for correspondence: Gerben Ferwerda, MD, PhD, Laboratory of Pediatric Infectious Diseases, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. E-mail:

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