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Open Access Research

Decreased Toll-like receptor 8 expression and lower TNF-alpha synthesis in infants with acute RSV infection

Kreso Bendelja1*, Valerija Vojvoda1, Neda Aberle2, Jasna Cepin-Bogovic3, Alenka Gagro3, Gordana Mlinaric-Galinovic4 and Sabina Rabatic1

Author Affiliations

1 Department of Cellular Immunology, Institute of Immunology, Zagreb, Croatia

2 Department of Pediatrics, General Hospital "Dr. Josip Benčević", Slavonski Brod, Croatia

3 Department of Pulmonology, Allergology, Immunology and Rheumatology, University Children's Hospital, Zagreb, Croatia

4 Department of Virology, Croatian National Institute of Public Health, Zagreb, Croatia

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Respiratory Research 2010, 11:143  doi:10.1186/1465-9921-11-143

Published: 14 October 2010

Abstract

Background

Toll-like receptors (TLRs) are part of the innate immune system, able to recognize pathogen-associated molecular patterns and activate immune system upon pathogen challenge. Respiratory syncytial virus (RSV) is a RNA virus particularly detrimental in infancy. It could cause severe lower respiratory tract disease and recurrent infections related to inadequate development of anti-viral immunity. The reason could be inadequate multiple TLRs engagement, including TLR8 in recognition of single-stranded viral RNA and diminished synthesis of inflammatory mediators due to a lower expression.

Methods

Intracellular TLR8 expression in peripheral blood monocytes from RSV-infected infants was profiled and compared to healthy adults and age matched controls. Whether the observed difference in TLR8 expression is a transitory effect, infants in convalescent phase (4-6 weeks later) were retested. Specific TLR8-mediated TNF-α production in monocytes during an acute and convalescent phase was analyzed.

Results

RSV-infected and healthy infants had lower percentage of TLR8-expressing monocytes than healthy adults whereas decreased of TLR8 protein levels were detected only for RSV-infected infant group. Lower protein levels of TLR8 in monocytes from RSV-infected infants, compared to healthy infants, negatively correlated with respiratory frequency and resulted in lower TNF-α synthesis upon a specific TLR8 stimulation. In the convalescent phase, levels of TLR8 increased, accompanied by increased TNF-α synthesis compared to acute infection.

Conclusions

Lower TLR8 expression observed in monocytes, during an acute RSV infection, might have a dampening impact on early anti-viral cytokine production necessary to control RSV replication, and subsequently initiate an adaptive Th1 type immune response leading to severe disease in infected infants.