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.
Highlights
Crohn’s disease (CD) is a chronic relapsing inflammatory condition of the gastrointestinal tract with increased production of Th1 cells [1]
To investigate whether nuclear factor erythroid 2-related factor-2 (Nrf2) is involved in M2 polarization induced by T. spiralis ES, we compared the polarization of ES–treated macrophages from wild type (WT) mice and Nrf2 KO mice
Our results showed that ES increased the expression of Arginase-1 (Arg1) in WT macrophages but the enhanced expression of Arg1 and CD206 (M2 markers) induced by ES was decreased in Nrf2 KO macrophages (Figures 1B, 2C, D)
Summary
Crohn’s disease (CD) is a chronic relapsing inflammatory condition of the gastrointestinal tract with increased production of Th1 cells [1]. Countries where helminth infection are endemic have a lower incidence of CD than non-endemic countries, and there have been interesting reports of the beneficial effects of helminths in CD patients [2], indicating that the regulatory effect of eliminating helminths often leads to imbalances in the immune system and increases immune-mediated diseases [3]. Several studies in animals and clinical trials provide strong evidence that helminth can downregulate CD –specific immune responses [3]. This kind of therapy is hard to accept for patients because of the fear of helminths. Helminths alleviate colitis through polarization of alternatively activated macrophages (M2) [4], which mediate Th2 type responses, contributing to suppression of Th1 type response [5]. Trichinella spiralis muscle larval excretory/secretory (MLES) products induce M2, which can ameliorate inflammation of colitis [9]
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