engleski

Increased TARC and IP-10 levels in acute RSV infection deplete CCR4+ and CXCR3+ CD8 T cells from peripheral blood

Infants, with their undeveloped immune system, are prone to severe respiratory syncytial virus (RSV) infections. RSV can skew antiviral type-1 to less effective type-2 immune reaction. Lymphocyte accumulation in the lungs during RSV infection is mediated by type-1 chemokines (IP-10, MIG and fractalkine) through binding of CXCR3 and CX3CR1. Opposing type-2 chemokines (TARC and MDC) are responsible for migration of CCR4-positive lymphocytes involved in allergic immune responses. We postulate that RSV-infected infants produce elevated type-2 chemokines which compromise antiviral response. PBMCs were isolated from RSV- and adenovirus/influenza-infected infants and age- matched healthy controls. Samples from RSV- infected infants were recollected 4-6 weeks after first sampling. PBMCs were simultaneously stained for chemokine receptors (CCR4, CXCR3 or CX3CR1) and lymphocyte subpopulation markers. Serum chemokines (TARC, MDC, IP-10, MIG, fractalkline) were determined by ELISA. Acute respiratory infection in infants was accompanied by lower percentage of CCR4+ T cells compared to healthy infants, with marginal tendency of lower CXCR3+ and CX3CR1+ T cells in the periphery. Significant reduction of CD8+ T cells bearing CCR4, CXCR3 and CX3CR1 was observed in all infected infants. Different frequencies of CXCR3+ CD8+ T cells distinguished RSV infected from infants suffering from other viral respiratory infections. Interestingly, higher percentages of B cells from infected infants expressed CCR4, CXCR3 and CX3CR1. RSV infection was accompanied by higher serum IP- 10 and TARC levels than in other respiratory infections and healthy controls. Moreover, TARC levels negatively correlated with acute clinical findings, while IP-10 levels were inversely related to disease severity. In conclusion, depletion of CCR4+ and CXCR3+ CD8 T cells from peripheral blood in RSV infection might be result of efflux to the lungs, orchestrated by increased TARC and IP-10 levels. Higher percentages of CCR4+, CXCR3+ and CX3CR1+ B cells in peripheral blood of RSV infected infants indicate an increased activation and active role for B cells during infection. Observed mixed type of chemokine production and receptor expression on T and B cells compromise effective anti-RSV response and could be related to allergic asthma development.

RSV; chemokine; chemokine receptors; infants; IP-10; TARC; CD8 T cells; CXCR3; CX3CR1; CCR4

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