Abstract
We inoculated BALB/c mice deficient in STAT6
(STAT6
−/−
) and their wild-type (wt) littermates
(STAT6
+/+
) with the natural mouse pathogen, ectromelia
virus (EV). STAT6
−/−
mice exhibited increased resistance
to generalized infection with EV when compared with
STAT6
+/+
mice. In the spleens and lymph nodes of
STAT6
−/−
mice, T helper 1 (Th1) cytokines were induced at
earlier time points and at higher levels postinfection when compared
with those in STAT6
+/+
mice. Elevated levels of NO were
evident in plasma and splenocyte 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 genetically susceptible BALB/c 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.