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Published on: May 31, 2018
IL-2 induces expression and secretion of IFN-gamma in murine peritoneal macrophages
Patrizia Puddu1, Maria Carollo, Immacolata Pietraforte
1Department of Cell Biology and Neurosciences, Viale Regina Elena 299, 00161 Rome, Italy.
Abstract:
We investigated the effect of interleukin (IL)-2, a T cell growth factor capable of activating certain macrophage functions, on interferon (IFN)-gamma expression in resting mouse peritoneal macrophages (PM). IL-2 addition to PM from different mouse strains up-modulated IFN-gamma mRNA and protein secretion. It is notable that endogenous type I and II IFNs did not play any role in the IL-2-mediated effect, as comparable levels of secreted IFN-gamma were observed upon IL-2 stimulation of PM from deficient mice. In contrast, endogenous IFN-gamma was requested for the IL-12-induced IFN-gamma production. It is interesting that blocking of each component of the IL-2 receptor (IL-2R) by neutralizing antibodies almost completely abolished IL-2-induced IFN-gamma production, suggesting that all IL-2R chains contribute to the PM biological response to IL-2. The simultaneous treatment of PM with IL-2 and IL-12 resulted in a higher IFN-gamma secretion with respect to that obtained upon treatment with IL-2 or IL-12 alone. It is notable that IFN-gamma protein was expressed intracellularly in the majority of cells exhibiting a macrophage phenotype (i.e., F4/80+) and was secreted upon IL-2 stimulation. Overall, these findings demonstrate that IL-2 regulates at different levels IFN-gamma expression in macrophages, highlighting the crucial role of these cells and their regulated responsiveness to key cytokines in the cross-talk between innate and adaptive immunity.
Insights
Interleukin-2 (IL-2) enhances interferon-gamma (IFN-gamma) production in macrophages. This cytokine signaling is crucial for macrophage communication within the immune system.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Macrophages are key immune cells involved in innate and adaptive immunity.
- Interferon-gamma (IFN-gamma) is a critical cytokine for immune responses.
- Interleukin-2 (IL-2) is known as a T cell growth factor with potential effects on other immune cells.
Purpose of the Study:
- To investigate the effect of IL-2 on IFN-gamma expression in mouse peritoneal macrophages (PM).
- To elucidate the role of IL-2 receptor (IL-2R) components and endogenous IFNs in IL-2-mediated IFN-gamma production.
- To explore the combined effects of IL-2 and IL-12 on macrophage IFN-gamma secretion.
Main Methods:
- Stimulation of mouse peritoneal macrophages (PM) with IL-2 and/or IL-12.
- Analysis of IFN-gamma mRNA and protein levels.
- Use of knockout mice deficient in type I/II IFNs.
- Blocking of IL-2 receptor (IL-2R) chains using neutralizing antibodies.
- Intracellular and secreted IFN-gamma detection in F4/80+ macrophages.
Main Results:
- IL-2 significantly up-modulated IFN-gamma mRNA and protein secretion in PM.
- Endogenous type I and II IFNs were not required for IL-2-mediated IFN-gamma production.
- Blocking IL-2R chains abolished IL-2-induced IFN-gamma production, indicating the importance of all IL-2R components.
- Combined IL-2 and IL-12 treatment resulted in synergistic enhancement of IFN-gamma secretion.
- IL-2 stimulation led to the secretion of intracellularly expressed IFN-gamma in macrophages.
Conclusions:
- IL-2 regulates IFN-gamma expression in macrophages at multiple levels.
- Macrophages play a vital role in immune cross-talk, influenced by cytokines like IL-2.
- The IL-2 receptor signaling pathway is essential for IL-2's effect on macrophage IFN-gamma production.
