Enhanced resistance in STAT6-deficient mice to infection with ectromelia virus.
نویسندگان
چکیده
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.
منابع مشابه
Obligatory requirement for antibody in recovery from a primary poxvirus infection.
To understand the correlates of protective immunity against primary variola virus infection in humans, we have used the well-characterized mousepox model. This is an excellent surrogate small-animal model for smallpox in which the disease is caused by infection with the closely related orthopoxvirus, ectromelia virus. Similarities between the two infections include virus replication and transmi...
متن کاملIdentification of nitric oxide synthase 2 as an innate resistance locus against ectromelia virus infection.
To assess whether nitric oxide synthase 2 (NOS2) fulfills the criteria of an innate resistance locus against an acute viral infection, we inoculated genetically deficient NOS2-/- mice with virulent ectromelia virus (EV), the causative agent of mousepox. NOS2-/- mice proved highly susceptible to EV yet showed no diminution in other well-characterized anti-EV immune responses, i.e. , gamma interf...
متن کاملTrypanosoma cruzi Mice to Infection with and Enhanced Resistance in Stat6-Deficient Increased Susceptibility of Stat4-Deficient
متن کامل
Mechanisms determining innate resistance to ectromelia virus infection in C57BL mice.
The mechanism for innate resistance to ectromelia virus, which is controlled by a single gene in C57BL mice, was investigated. The cells or factors involved appear to be radioresistant and to impose an early barrier to viral penetration and spread via lymphatics or blood to the target organs, i.e., liver and spleen.
متن کاملSurviving Mousepox Infection Requires the Complement System
Poxviruses subvert the host immune response by producing immunomodulatory proteins, including a complement regulatory protein. Ectromelia virus provides a mouse model for smallpox where the virus and the host's immune response have co-evolved. Using this model, our study investigated the role of the complement system during a poxvirus infection. By multiple inoculation routes, ectromelia virus ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 98 12 شماره
صفحات -
تاریخ انتشار 2001