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Nrf2 Participates in M2 Polarization by Trichinella spiralis to Alleviate TNBS-Induced Colitis in Mice
Xuemin Jin1, Xue Bai1, Ying Zhao2
1Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China.
Abstract:
Trichinella spiralis induced alternative activated macrophages (M2), leading to protect against Crohn's disease, known as Th1 -related inflammation, which enhances oxidative stress in the host. However, the relationship of oxidative stress and T. spiralis -mediated immune response is still unknown. In our study, we showed that nuclear factor erythroid 2-related factor-2 (Nrf2), a key transcription factor in antioxidant, participated in M2 polarization induced by T. spiralis muscle larval excretory/secretory (ES) products in vitro. ES -treated M2 were injected intravenously after TNBS challenge and we demonstrated that ES-M could alleviate the severity of the colitis in mice. Adoptive transfer of ES -treated M2 decreased the level of IFN-γ and increased the levels of IL-4 and IL-10 in vivo. However, the capacity of ES -treated Nrf2 KO macrophages to treat colitis was dramatically impaired. ES -treated Nrf2 KO macrophages was insufficient to result in the elevated levels of IL-4 and IL-10. These findings indicate that Nrf2 was required for M2 polarization induced by T. spiralis ES to alleviate colitis in mice.
Insights
Trichinella spiralis excretory/secretory products induce antioxidant factor Nrf2 in M2 macrophages, which are crucial for alleviating colitis in mice. Nrf2 is essential for this protective immune response against inflammatory bowel disease.
Area of Science:
- Immunology
- Parasitology
- Gastroenterology
Background:
- Trichinella spiralis infection induces alternative activated macrophages (M2), offering protection against Crohn's disease.
- The role of oxidative stress in T. spiralis-mediated immune responses, particularly in relation to M2 polarization and colitis, remains unclear.
Purpose of the Study:
- To investigate the involvement of nuclear factor erythroid 2-related factor-2 (Nrf2) in T. spiralis-induced M2 polarization.
- To determine the therapeutic potential of T. spiralis excretory/secretory (ES) products-treated M2 macrophages in a mouse model of colitis, focusing on the role of Nrf2.
Main Methods:
- In vitro M2 polarization induced by T. spiralis muscle larval ES products.
- In vivo administration of ES-treated M2 macrophages in TNBS-induced colitis mouse model.
- Assessment of inflammatory markers (IFN-γ, IL-4, IL-10) and the impact of Nrf2 knockout (KO) macrophages on colitis severity.
Main Results:
- T. spiralis ES products induced M2 polarization, with Nrf2 identified as a key transcription factor in this process.
- Adoptive transfer of ES-treated M2 macrophages alleviated colitis severity in mice by decreasing IFN-γ and increasing IL-4 and IL-10.
- Nrf2 deficiency in ES-treated M2 macrophages significantly impaired their ability to treat colitis and restore IL-4 and IL-10 levels.
Conclusions:
- Nrf2 is essential for T. spiralis ES-induced M2 polarization.
- Nrf2-dependent M2 polarization mediated by T. spiralis ES products holds therapeutic potential for inflammatory bowel diseases like colitis.
