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Updated: May 1, 2026

Deciphering the Molecular Mechanism and Function of Pore-Forming Toxins Using Leishmania major
Published on: October 28, 2022
Human polymorphonuclear leukocytes produce cytokines in response to Leishmania major promastigotes
Alireza Keyhani1, Farhad Riazi-Rad, Saeed Reza Pakzad
1Islamic Azad University-Pharmaceutical Sciences Branch (IAUPS), Tehran, Iran.
Abstract:
Polymorphonuclear leukocytes (PMN) release cytokines that may influence the development of the subsequent adaptive immune response. Little is known about cytokines produced by human PMN in response to Leishmania (L.). In this study, mRNA expression of Interleukin (IL)-12p40, IL-12p35, Interferon (IFN)-γ, transforming growth factor (TGF)-β, IL-1, and IL-4 in PMN of volunteers stimulated with L. major promastigotes has been investigated by real-time PCR and the results were confirmed by flow cytometer. The results showed that L. major did not induce mRNA expression of IL12p40, IL12p35, IFN-γ, and TGF-β in PMN, while IL-1 and IL-4 mRNA were induced. Flow cytometry results confirmed no IFN-γ production by PMN with or without stimulation. IL-12p70 was present in untreated and L. major-treated PMN, and these cells release IL-12 following incubation with L. major. Significant amount of IL-1 even without treatment with promastigotes was detected in PMN. Moreover, the proportion of PMN, which produce IL-1 in response to L. major, was increased compared with the percent of unstimulated IL-1-producing PMN. The results showed the accumulation of small amounts of IL-4 in PMN after stimulation. In conclusion, our results indicate that IL-12 and IL-1 are pre-stored in human PMN, nor L. major induces IL-1 and IL-4, but not IL-12, IFN-γ, nor TGF-β expression in these cells.
Insights
Human polymorphonuclear leukocytes (PMN) produce Interleukin-1 (IL-1) and Interleukin-4 (IL-4) when exposed to Leishmania major. However, Leishmania major does not induce expression of IL-12, Interferon-gamma (IFN-γ), or TGF-β in PMN.
Area of Science:
- Immunology
- Cell Biology
Background:
- Polymorphonuclear leukocytes (PMN) are crucial innate immune cells.
- Cytokine production by PMN influences adaptive immunity.
- The role of human PMN in Leishmania infection response is not fully understood.
Purpose of the Study:
- To investigate cytokine mRNA expression in human PMN stimulated with Leishmania major.
- To determine the production of specific cytokines (IL-12p40, IL-12p35, IFN-γ, TGF-β, IL-1, IL-4) by PMN in response to Leishmania major.
Main Methods:
- Real-time PCR was used to measure mRNA expression of selected cytokines in PMN.
- Flow cytometry confirmed cytokine production.
- Human PMN were stimulated with Leishmania major promastigotes.
Main Results:
- Leishmania major did not induce mRNA expression of IL-12p40, IL-12p35, IFN-γ, or TGF-β in PMN.
- IL-1 and IL-4 mRNA expression were induced by Leishmania major.
- IFN-γ production was not detected in PMN, with or without stimulation.
- IL-12p70 was present in both untreated and treated PMN, indicating pre-stored IL-12.
- IL-1 was significantly detected in unstimulated PMN and its production increased upon Leishmania major stimulation.
- Small amounts of IL-4 accumulated in PMN after stimulation.
Conclusions:
- Human PMN pre-store IL-12 and IL-1.
- Leishmania major induces IL-1 and IL-4 expression in PMN.
- Leishmania major does not induce IL-12, IFN-γ, or TGF-β expression in human PMN.
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