engleski

Innate immunity to respiratory syncytial virus: antiviral response mediated by Toll-like receptors.

Innate immunity is important part of immune system with ability to recognize and act (neutralize) upon pathogen challenge. Infants are particularly sensitive to different viral infections with emphasized detrimental effect of respiratory syncytial virus (RSV) induced recurrent infections in infancy related to inadequate anti-viral immunity post-infection. Toll-like receptors (TLRs) are part of the immune system able to recognize and activate immune system upon pathogen challenge. Previous studies demonstrated a specific engagement of RSV fusion protein with TLR4. Other members of TLR-family (TLR3, TLR7, and TLR8) that recognize genomic viral RNA molecules could also have a significant role in the initiation of antiviral control mechanisms and development of specific immune reaction. Possible explanation for frequent RSV re-infections in infancy could be inadequate TLR3, TLR7 and TLR8 engagement in innate immunity responses resulting in inability to control RSV replication, lower inflammatory cytokines synthesis, and development of inadequate specific anti-RSV immune response. In our study specific monoclonal antibodies against human TLR7 and TLR8 molecules were used to determine expression profile of monocytes and NK cells from healthy adults, healthy and RSV-infected infants by flow cytometry. We have found that RSV-infected infants had lower percentages of TLR8-expressing monocytes and NK cells than healthy controls. Moreover, MFI of TLR8 in both leukocyte populations was lower in diseased infants. Although expression of TLR7 in monocytes didn’ t statistically differ between healthy and infected infants, a tendency of lower percentages of TLR7-positive monocytes was observed. The comparison of TLR7 and TLR8 expression between different age groups revealed lower expression in monocytes from peripheral blood of infants (diseased and healthy group) than in monocytes from healthy adults. Surprisingly, percentages of NK cells bearing TLR8 and intensity of TLR8 expression were higher in healthy infants than healthy adults. In conclusion, lower expression of TLR’ s recognizing RSV in infants stresses out inadequate early antiviral and innate immune mechanisms responsible for the RSV replication control and generation an effective immune response.

innate immunity; toll-like receptors; TLR; TLR3; TLR7; TLR8; RSV

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