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Excretory/Secretory Products From Trichinella spiralis Adult Worms Attenuated DSS-Induced Colitis in Mice by Driving PD-1-Mediated M2 Macrophage Polarization.
- Source :
-
Frontiers in immunology [Front Immunol] 2020 Oct 02; Vol. 11, pp. 563784. Date of Electronic Publication: 2020 Oct 02 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- Helminth-modulated macrophages contribute to attenuating inflammation in inflammatory bowel diseases. The programmed death 1 (PD-1) plays an important role in macrophage polarization and is essential in the maintenance of immune system homeostasis. Here, we investigate the role of PD-1-mediated polarization of M2 macrophages and the protective effects of excretory/secretory products from Trichinella spiralis adult worms (AES) on DSS-induced colitis in mice. Colitis in mice was induced by oral administration of dextran sodium sulfate (DSS) daily. Mice with DSS-induced colitis were treated with T. spiralis AES intraperitoneally, and pathological manifestations were evaluated. Macrophages in mice were depleted with liposomal clodronate. Markers for M1-type (iNOS, TNF-α) and M2-type (CD206, Arg-1) macrophages were detected by qRT-PCR and flow cytometry. Macrophage expression of PD-1 was quantified by flow cytometry; RAW 264.7 cells and peritoneal macrophages were used for in vitro tests, and PD-1 gene knockout mice were used for in vivo investigation of the role of PD-1 in AES-induced M2 macrophage polarization. Macrophage depletion was found to reduce DSS-induced colitis in mice. Treatment with T. spiralis AES significantly increased macrophage expression of CD206 and Arg-1 and simultaneously attenuated colitis severity. We found T. spiralis AES to enhance M2 macrophage polarization; these findings were confirmed studying in vitro cultures of RAW264.7 cells and peritoneal macrophages from mice. Further experimentation revealed that AES upregulated PD-1 expression, primarily on M2 macrophages expressing CD206. The AES-induced M2 polarization was found to be decreased in PD-1 deficient macrophages, and the therapeutic effects of AES on colitis was reduced in PD-1 knockout mice. In conclusion, the protective effects of T. spiralis AES on DSS-induced colitis were found to associate with PD-1 upregulation and M2 macrophage polarization. Thus, PD-1-mediated M2 macrophage polarization is a key mechanism of helminth-induced modulation of the host immune system.<br /> (Copyright © 2020 Wang, Hao, Zhuang, Zhan, Sun, Huang, Cheng and Zhu.)
- Subjects :
- Animals
Colitis immunology
Disease Models, Animal
Female
Gene Knockout Techniques
Macrophage Activation
Male
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
Mice, Knockout
Programmed Cell Death 1 Receptor genetics
RAW 264.7 Cells
Rats
Bodily Secretions
Cell Polarity genetics
Colitis chemically induced
Colitis therapy
Dextran Sulfate adverse effects
Macrophages, Peritoneal immunology
Programmed Cell Death 1 Receptor metabolism
Trichinella spiralis metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 11
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 33117347
- Full Text :
- https://doi.org/10.3389/fimmu.2020.563784