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


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-? 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-? synthesis upon a specific TLR8 stimulation. In the convalescent phase, levels of TLR8 increased, accompanied by increased TNF-? 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.

SUBMITTER: Bendelja K 

PROVIDER: S-EPMC2974671 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Bendelja Kreso K   Vojvoda Valerija V   Aberle Neda N   Cepin-Bogovic Jasna J   Gagro Alenka A   Mlinaric-Galinovic Gordana G   Rabatic Sabina S  

Respiratory research 20101014


<h4>Background</h4>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 recogniti  ...[more]

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