Decreased Toll-like receptor 8 expression and lower TNF-α synthesis in infants with acute RSV infection.
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.
Department of Cellular Immunology, Institute of Immunology, Zagreb, Croatia. kbendelja@gmail.com
Kreso
K
Bendelja
Valerija
V
Vojvoda
Neda
N
Aberle
Jasna
J
Cepin-Bogovic
Alenka
A
Gagro
Gordana
G
Mlinaric-Galinovic
Sabina
S
Rabatic
D000208:Acute Disease; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009000:Monocytes / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000378:metabolism*; D051200:Toll-Like Receptor 8 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*
D015415:Biomarkers; C495349:TLR8 protein, human; D051200:Toll-Like Receptor 8; D014409:Tumor Necrosis Factor-alpha