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Regulation of IL-18 expression in virus infection
1Department of Virology, National Public Health Institute, Helsinki, Finland. jaana.pirhonen@ktl.fi
Abstract:
Since its discovery as an interferon (IFN)-gamma-inducing factor, it has become evident that interleukin (IL)-18 plays a crucial role in the generation of protective immunity against microbial infections. Macrophages are the major source of biologically active IL-18, and they express constitutively IL-18 mRNA and proIL-18 protein. Microbial infections enhance the IL-18 gene expression in macrophages but post-translational processing of proIL-18, rather than transcriptional activation, is predominant in the regulation of IL-18 secretion. This review summarizes the current knowledge of proinflammatory and immunomodulatory properties of IL-18, and focuses on the role of caspases in the proteolytic activation of IL-18 in response to virus infection.
Insights
Interleukin-18 (IL-18) is vital for immunity against infections. Its secretion by macrophages relies on processing the proIL-18 protein, especially during viral infections, rather than just gene expression.
Area of Science:
- Immunology
- Molecular Biology
- Microbiology
Background:
- Interleukin-18 (IL-18) is recognized for its role in inducing interferon-gamma (IFN-γ).
- Macrophages are primary producers of IL-18, constitutively expressing IL-18 mRNA and proIL-18.
- Microbial infections modulate IL-18 expression in macrophages.
Purpose of the Study:
- To review the proinflammatory and immunomodulatory functions of IL-18.
- To highlight the regulatory mechanisms of IL-18 secretion, focusing on post-translational processing.
- To examine the specific role of caspases in IL-18 activation during viral infections.
Main Methods:
- Literature review of existing research on IL-18.
- Analysis of studies on macrophage responses to microbial infections.
- Focus on molecular mechanisms of proIL-18 processing by caspases.
Main Results:
- IL-18 secretion is primarily regulated by the post-translational processing of proIL-18, not solely by gene expression.
- Caspases play a critical role in the proteolytic activation of IL-18.
- IL-18 contributes significantly to protective immunity against various microbial pathogens.
Conclusions:
- Post-translational modification of proIL-18 is a key regulatory step for IL-18 secretion.
- Caspase-mediated cleavage is essential for generating biologically active IL-18, particularly in response to viral challenges.
- IL-18 is a crucial cytokine for orchestrating effective immune responses against infections.