Enhanced resistance in STAT6-deficient mice to infection with ectromelia virus.
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.
Mahalingam
S
S
Division of Biochemistry and Molecular Biology, The John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia. Surendran.Mahalingam@anu.edu.au
Karupiah
G
G
Takeda
K
K
Akira
S
S
Matthaei
K I
KI
Foster
P S
PS
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004482:Ectromelia, Infectious / Q000276:immunology* / Q000473:pathology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D050800:STAT6 Transcription Factor; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D015534:Trans-Activators / Q000172:deficiency / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma