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U predavanju su prikazani vlastiti rezultati 10-godišnjih istraživanja u području imunologije RSV-infekcije.

Respiratory syncytial virus (RSV) is the most common pathogen of the lower respiratory tract in infants and toddlers. RSV surface glycoprotein G structurally and functionally mimics CX3C chemokine fractalkine, which signals through NF- kappaB and mediates capture from bloodstream, adhesion and activation of cells expressing its receptor, CX3CR1, and promotes their further migration. CX3CR1 is found on the surface of cytotoxic T lymphocytes (CTLs), which are considered to be major effector cells that clear the virus from the organism. However, when inappropriately activated, these cells could also augment the disease. To examine the relationship between RSV infection and the expression of CX3CR1 and effector functions of CTLs (assessed by perforin expression and IFN-gamma secretion), we obtained the peripheral blood samples of infants admitted to the hospital for RSV bronchiolitis, both in the acute and convalescence phase (n=12), and from their age- and gender-matched healthy controls (n=18). Perforin, IFN-gamma and CX3CR1 were determined by four-color flow cytometry, and NF-kappaB p50 and p65 binding activities of PBMC nuclear extract were measured by ELISA-based assay. The results showed that perforin and CX3CR1 expression was significantly lower in the convalescent phase of infected infants than in healthy controls. We found no significant difference in IFN-gamma secretion and NF-kappaB binding activity between two time-points in RSV- infected infants, or when compared to healthy controls. Infants with prolonged wheezing and therefore more severe disease presentation had higher acute-phase CX3CR1 levels in peripheral blood. These data might indicate that in addition to previously reported RSV-induced chemokine secretion, binding of RSV proteins to chemokine receptors can result in augmented inflammatory response during infection.

Respiratory syncytial virus (RSV) is the leading cause of serious lower respiratory tract illness in infants and young children. Approximately 80% of childhood bronchiolitis cases and 50% of infant pneumonias are attributable to RSV infection. RSV fusion (F) protein, responsible for the merging of RSV infected with adjacent uninfected epithelial cells, also stimulates cytokine production in monocytes through CD14 and Toll-like receptor 4 (TLR4). Another surface glycoprotein, protein G, functionally mimics CX3C chemokine fractalkine, regulator of cytotoxic effector lymphocytes' tissue migration. It has been shown in mice that RSV G glycoprotein modifies cytokine and chemokine expression, sensitizes for pulmonary eosinophilia and alters pulmonary leukocyte trafficking. In our present study we analyzed the expression of perforin, IFN-?, IL-4 and fractalkine receptor CX3CR1 on cytotoxic T lymphocytes (n=11), and TLR4 expression on monocytes. The samples were obtained from peripheral blood of acutely ill infants with bronchiolitis (aged from 2 weeks to 5 months) and 4-6 weeks after the resolution of the disease. The observed effects of RSV infection on the above listed cytokines and receptor expression will be discussed.