engleski

Type-1 and type-2 chemokine receptors on lung T cells during acute RSV infection in infants

Respiratory syncytial virus (RSV) is the most common seasonal viral pathogen in children by second year of life and in some cases it causes a severe respiratory disease. Frequent RSV reinfections and similarity of clinical findings with allergic asthma (airway hyper-responsiveness, wheezing) indicate development of mixed type- 1/type-2 immune response. Presence of IFN-γ/IL-4 in acute RSV infection could be confirmed by simultaneous production of type-1 associated (CXCL10) and type-2 associated (CCL17) chemokines, responsible for recruitment of activated CXCR3+ and CCR4+ T cells detected at higher percentages in the periphery of diseased infants indicating inadequate immune response. As CCR4 is not type-2 exclusive chemokine receptor, and could be found on different T cell types, addition of CRTh2 chemokine receptor analysis would contribute to more accurate type-2 immune response assessment. Moreover, most of conclusions regarding aberrant type of anti-RSV immune response in humans are extrapolated from peripheral blood analysis, and acquisition of bronchoalveolar lavage (BAL) samples of infected infants would provide unique insight into development of local immune response. BAL samples were obtained from infants hospitalized due to sever bronchiolitis or pneumonia caused by RSV (n=14) or other respiratory viruses (n=8) and bacterial pathogens (n=7) where bronchoscopy was clinically ascribed. Concentrations of chemokines CXCL10 and CCL17 were assessed using commercially available ELISA kits. Isolated cells were immunophenotyped for CD4 and CD8 T cell specific markers and specific chemokine receptors CXCR3, CCR4 and CRTh2. Cells were analysed on LSRII flow cytometer and data analysed using Statistica v7.0 software. BAL samples of all infected infants were found positive only for CXCL10, while CCL17 was undetectable regardless of pathogen. RSV infected infants had higher percentage CXCR3+ CD4 and CD8 T cells compared to other viral respiratory infections. High percentages of CCR4+ CD4 and CD8 T cells were also detected in RSV infected infants. Coexpression of CRTh2 chemokine receptor was detected on CCR4+ CD4 and CD8 T cells in RSV infected infants. The presence of type-2 immune response in lungs of RSV infected infants was confirmed in regards of higher expression of CCR4 and CRTh2 chemokine receptors on CD4 and CD8 T cells. Although CCL17 was not detected at the time of bronchoscopy, a high CXCL10 concentration implicates efficient tracking of antiviral and pro-inflammatory CXCR3+ T cell to the lungs. As CCL17 and CCR4 are, beside type-2 T cells, also involved in regulatory T cell (Treg) migration, undetectable CCL17 in RSV infected infants could explain more severe disease due to insufficient number of Treg cells in affected tissue.

RSV; BAL; chemokines; infants

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