engleski

High chemokine TARC and IP-10 levels in acute RSV infection

Objectives: Respiratory syncytial virus (RSV) causes lower respiratory tract infection (bronchiolitis) in newborns/infants directed by the mononuclear cell accumulation to the lungs. Undeveloped immune system in infants is considered to be cause of severe form of illness, although RSV itself has potential to skew the effective antiviral type-1 immune reaction to less effective type-2. Type-1 related chemokines (IP-10, MIG and fractalkine) predominantly induce migration of CXCR3 and CX3CR1 positive, type-1 profiled lymphocytes that are necessary to control viral infections. Opposing type-2 related chemokines (TARC and MDC) are responsible for migration of CCR4-positive type-2 lymphocytes involved in allergic immune responses. We postulate that RSV-infected infants produce elevated type-2 vs. type-1 cytokine-associated chemokines that compromise effective antiviral response. Methods: PMBC were isolated from blood samples of RSV-infected hospitalized infants (N=14), 6 infants infected with influenza and adenovirus, 9 age-matched healthy controls and from blood samples of 10 infants collected 4-6 weeks after first sampling. PBMC were simultaneously stained with mAb´s for chemokine receptors (CCR4, CXCR3, CX3CR1), and lymphocyte subpopulation markers. Multiparametric analyis was performed on LSRII flow cytometer. Frozen serum samples were used to measure soluble chemokine (TARC, MDC, IP-10, MIG, fractalkline, I-TAC, TSLP) concentration. Results: In acute phase of RSV- and other viruse-infected infants, the predominant chemokine in serum is IP-10. TARC is overproduced in RSV while fractalkine and MIG are predominant in acute influenza and adenovirus infections. Interestingly, 4-6 weeks after first sampling, serum levels of TARC, MDC, IP-10 and MIG increased even more in RSV-infected infants. In acute phase, higher percentages of B-lymphocytes and CTL's express CCR4, CXCR3 and CX3CR1 compared to healthy and other-viruses infected infants. In convalescent phase, percentages of CCR4-positive B-lymphocytes and CTL's didn't change while there was increase of CXCR3 expression. Conclusion: Mixed type of cytokine production during acute phase of RSV infection could be observed on both the chemokine and chemokine receptors level. Higher TARC concentration imposes type-2 immune reaction at inflammatory site that could lead to more pronounced RSV-driven inflammatory process with severe clinical findings since CCR4-positive lymphocytes contribute to type-2 cytokine synthesis and confront effective type-1 cytokine-driven antiviral immune reaction.

RSV; chemokine; infants; IP-10; MIG; TARC; MDC; fractalkine; CXCR3; CX3CR1; CCR4

nije evidentirano