The effects of murine cytomegalovirus infection on the expression of T H1/TH2 type cytokines and related transcription factor T-bet and GATA-3

Objective: To investigate the effects of murine cytomegalovirus infection on the expression of TH1/TH2 type cytokines and specific transcription factor T-bet/CATA-3 inducing their differentiation. Methods: A BALB/c mice model system of MCMV infection was established. Forty BALB/c mice were randomly divided into MCMV-infected group (n = 20) and blank controls group (n = 20). All experimental mice were sacrificed at 3, 5, 7, 14 days (n = 5 at each time point) after MCMV infection (p.i.). Hearts and spleens were removed under aseptic conditions. One part of each heart was processed with Bouin's fixative for histological examination. The other part for testing the expression levels of each heart was immediately forzen in liquid nitrogen and then stored at -80°C untill IFN-γ and IL-4 were measured by ELISA. Transcription factor T-bet and GATA-3 of spleen tissue were determined by Western blot analysis. Results: Levels of IFN-γ significantly rose on day 3 p.i., and then dropped to levels similar to those in uninfected mice on day 14 p.i.. Levels of IL-4 significantly increased on day 14 p.i.. Correspondingly, transcription factor T-bet significantly decreased on day 7 and day 14 p.i., and transcription factor GATA-3 significantly increased on day 7 and day 14 p.i.. Meanwhile, a mixed cellular infiltrate composed of polymorphonuclear neutrophils and mononuclear lymphocytes was observed on days 3, which reached a peak on day 7 p.i.. Seurm cTnI levels were elevated on day 3 p.i., reaching a peak at day 7 p.i.. Conclusion: MCMV infection markedly down-modulated the expression of IFN-γ and T-bet, and significantly up-regulated the expression of IL-4 and GATA-3, indicating CMV infection led to the disequilibrium of T H1/TH2 cells' differentiation and their cytokines' expression, which is likely to suppress the functions of cellular immunity in the infected host and to be one of the reasons of CMV escaping the attack of body's specific cellular immunity so that causing persistent or latent infections and even leading to diseases under the certain conditions.