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.
History
Publication title
National Academy of Sciences of The United States of America. Proceedings
Volume
98
Issue
12
Pagination
6812-6817
ISSN
0027-8424
Department/School
Tasmanian School of Medicine
Publisher
Natl Acad Sciences
Place of publication
2101 Constitution Ave Nw, Washington, USA, Dc, 20418
Rights statement
Copyright 2001 the authors
Repository Status
Restricted
Socio-economic Objectives
Prevention of human diseases and conditions; Treatment of human diseases and conditions