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

We inoculated BALByc mice deficient in STAT6 (STAT62/2) and their wild-type (wt) littermates (STAT61/1) with the natural mouse pathogen, ectromelia virus (EV). STAT62/2 mice exhibited increased resistance to generalized infection with EV when compared with STAT61/1 mice. In the spleens and lymph nodes of STAT62/2 mice, T helper 1 (Th1) cytokines were induced at earlier time points and at higher levels postinfection when compared with those in STAT61/1 mice. Elevated levels of NO were evident in plasma and splenocyte cultures of EV-infected STAT62/2 mice in comparison with STAT61/1 mice. The induction of high levels of Th1 cytokines in the mutant mice correlated with a strong natural killer cell response. We demonstrate in genetically susceptible BALByc mice that the STAT6 locus is critical for progression of EV infection. Furthermore, in the absence of this transcription factor, the immune system defaults toward a protective Th1-like response, conferring pronounced resistance to EV infection and disease progression.