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.
Bendelja
Kreso
K
Department of Cellular Immunology, Institute of Immunology, Zagreb, Croatia. kbendelja@gmail.com
Vojvoda
Valerija
V
Aberle
Neda
N
Cepin-Bogovic
Jasna
J
Gagro
Alenka
A
Mlinaric-Galinovic
Gordana
G
Rabatic
Sabina
S
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