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Type 1 and type 2 cytokines in antiviral defense
1Division of Immunology and Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra ACT, Australia. guna.karupiah@anu.edu.au
Abstract:
Ectromelia virus (EV) is a natural mouse pathogen that causes a generalized infection termed mousepox, which, in the genetically resistant C57BL/6 (B6) mouse, is an inapparent disease. In contrast, BALB/c and A strain mice are highly susceptible; one infectious virus particle can result in 100% mortality. The contribution of cytokines in the induction of protective immune responses and recovery from infection with EV in B6, BALB/c and A strain mice have been. In the spleen and lymph node (LN) of resistant B6 mice, IL-2, IFN-gamma and TNF-alpha were induced rapidly with large numbers of cells producing these cytokines. All three cytokines were virtually absent in BALB/c and A strain mice. No significant differences were found in the numbers of IL-4 producing cells in the spleen or LN of both resistant and susceptible mice. IFN-gamma-producing cells were detected in the spleen but not in the lymph node whereas IL-2-producing cells were detected only in the lymph node of B6 mice. Despite significant increases in the IFN-gamma mRNA levels in the LN of B6 mice, no protein was detected by immunocytochemistry. The mRNA levels of IL-2, TNF-alpha and IL-12 were also rapidly upregulated in LN of B6 mice. The rapid induction of type I cytokines strongly correlated with a potent antiviral CTL response in B6 mice. The absence of these cytokines also correlated with a complete absence or delayed induction of CTL responses to EV in both the BALB/c and A strain mice. IFN-gamma gene knock out mice on a B6 background were as susceptible to EV as the BALB/c and A strain mice.
Insights
Resistant mice rapidly produce key cytokines like IL-2, IFN-gamma, and TNF-alpha, crucial for controlling Ectromelia virus (EV) infection. Susceptible mice lack these cytokines, leading to severe mousepox and high mortality.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- Ectromelia virus (EV) causes mousepox, with varying severity in different mouse strains.
- C57BL/6 (B6) mice are genetically resistant, experiencing inapparent disease, while BALB/c and A strains are highly susceptible, leading to 100% mortality.
Purpose of the Study:
- To investigate the role of cytokines in the immune response to Ectromelia virus infection in resistant and susceptible mouse strains.
- To understand the correlation between cytokine production, T-cell responses, and disease outcome.
Main Methods:
- Comparison of cytokine production (IL-2, IFN-gamma, TNF-alpha, IL-4) in spleen and lymph nodes of B6, BALB/c, and A strain mice post-EV infection.
- Analysis of cytokine mRNA and protein levels.
- Assessment of cytotoxic T lymphocyte (CTL) responses.
- Evaluation of Ectromelia virus susceptibility in IFN-gamma gene knockout mice.
Main Results:
- Resistant B6 mice showed rapid induction of IL-2, IFN-gamma, and TNF-alpha in spleen and lymph nodes.
- Susceptible BALB/c and A strain mice had absent or significantly delayed production of these key cytokines.
- A strong correlation was observed between rapid type I cytokine induction and potent antiviral CTL responses in B6 mice.
- IFN-gamma knockout mice on a B6 background exhibited high susceptibility to EV, similar to BALB/c and A strains.
Conclusions:
- Rapid induction of IL-2, IFN-gamma, and TNF-alpha is critical for protective immunity and recovery from Ectromelia virus infection in resistant mice.
- The absence of these cytokines contributes to susceptibility and high mortality in BALB/c and A strain mice.
- IFN-gamma plays a vital role in controlling Ectromelia virus infection.