Enhanced resistance in STAT6-deficient mice to infection with ectromelia virus

We inoculated BALB/c mice deficient in STAT6 (STAT6(-/-)) and their wild-ty pe (wt) littermates (STAT6(+/+)) with the natural mouse pathogen, ectromeli a virus (EV). STAT6(-/-) mice exhibited increased resistance to generalized infection with EV when compared with STAT6(+/+) mice. In the spleens and l ymph nodes of STAT6(-/-) mice, T helper 1 (Th1) cytokines were induced at e arlier time points and at higher levels postinfection when compared with th ose in STAT6(+/+) mice. Elevated levels of NO were evident in plasma and sp lenocyte cultures of EV-infected STAT6(-/-) mice in comparison with STAT6(/+) mice. The induction of high levels of Th1 cytokines in the mutant mice correlated with a strong natural killer cell response. We demonstrate in ge netically susceptible BALB/c mice that the STAT6 locus is critical for prog ression of EV infection. Furthermore, in the absence of this transcription factor, the immune system defaults toward a protective Th1-like response, c onferring pronounced resistance to EV infection and disease progression.