PD-L2 Blockade Exacerbates Liver Lesion in Mice Infected with <i>Capillaria hepatica</i> through Reducing Alternatively Activated Macrophages
<i>Capillaria hepatica</i> is a seriously neglected zoonotic parasite, which infects the liver of mammalian hosts, causing fibrosis or even hepatic failure. At present, the immune responses elicited by <i>C. hepatica</i> are not fully understood, and the role(s) of the progra...
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MDPI AG
2023-01-01
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| Series: | Tropical Medicine and Infectious Disease |
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| Online Access: | https://www.mdpi.com/2414-6366/8/1/46 |
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| author | Minjun Huang Xiaoli Li Xiaoyan Zheng Fei Wang Yang Zou Lei Wang |
| author_facet | Minjun Huang Xiaoli Li Xiaoyan Zheng Fei Wang Yang Zou Lei Wang |
| author_sort | Minjun Huang |
| collection | DOAJ |
| description | <i>Capillaria hepatica</i> is a seriously neglected zoonotic parasite, which infects the liver of mammalian hosts, causing fibrosis or even hepatic failure. At present, the immune responses elicited by <i>C. hepatica</i> are not fully understood, and the role(s) of the programmed death 1 (PD-1) signaling pathway in the context of <i>C. hepatica</i>-induced pathology are not known. In this study, we identify that the late stage of infection with <i>C. hepatica</i>—especially the egg-derived antigens—modulates the host immune responses to promote alternatively activated macrophage (M2) polarization and programmed death ligand 2 (PD-L2) expression. The PD-L2-expressing alternatively activated M2 macrophages play an important role in maintaining Th2-biased regulatory immune responses, which may facilitate the survival of parasitic worms or eggs within the infected liver and reduce the liver pathology caused by the egg granulomas. Treatment with anti-PD-L2 antibody had no effect on the survival of parasitic eggs but deteriorated the pathology of egg granulomas. The obtained results suggest that PD-1/PD-L2 signaling, which is involved in alternative macrophage polarization, determines the immune response pattern and the immunopathology, consequently determining the outcome of the parasitic infection. |
| first_indexed | 2024-03-09T11:05:09Z |
| format | Article |
| id | doaj.art-726d21195c9748deb0a1f6f1b1c17a55 |
| institution | Directory Open Access Journal |
| issn | 2414-6366 |
| language | English |
| last_indexed | 2024-03-09T11:05:09Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Tropical Medicine and Infectious Disease |
| spelling | doaj.art-726d21195c9748deb0a1f6f1b1c17a552023-12-01T00:58:21ZengMDPI AGTropical Medicine and Infectious Disease2414-63662023-01-01814610.3390/tropicalmed8010046PD-L2 Blockade Exacerbates Liver Lesion in Mice Infected with <i>Capillaria hepatica</i> through Reducing Alternatively Activated MacrophagesMinjun Huang0Xiaoli Li1Xiaoyan Zheng2Fei Wang3Yang Zou4Lei Wang5Beijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, ChinaBeijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, ChinaBeijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, ChinaBeijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, ChinaBeijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, ChinaBeijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China<i>Capillaria hepatica</i> is a seriously neglected zoonotic parasite, which infects the liver of mammalian hosts, causing fibrosis or even hepatic failure. At present, the immune responses elicited by <i>C. hepatica</i> are not fully understood, and the role(s) of the programmed death 1 (PD-1) signaling pathway in the context of <i>C. hepatica</i>-induced pathology are not known. In this study, we identify that the late stage of infection with <i>C. hepatica</i>—especially the egg-derived antigens—modulates the host immune responses to promote alternatively activated macrophage (M2) polarization and programmed death ligand 2 (PD-L2) expression. The PD-L2-expressing alternatively activated M2 macrophages play an important role in maintaining Th2-biased regulatory immune responses, which may facilitate the survival of parasitic worms or eggs within the infected liver and reduce the liver pathology caused by the egg granulomas. Treatment with anti-PD-L2 antibody had no effect on the survival of parasitic eggs but deteriorated the pathology of egg granulomas. The obtained results suggest that PD-1/PD-L2 signaling, which is involved in alternative macrophage polarization, determines the immune response pattern and the immunopathology, consequently determining the outcome of the parasitic infection.https://www.mdpi.com/2414-6366/8/1/46alternatively activated macrophages<i>Capillaria hepatica</i>immunomodulationprogrammed death ligand 2 |
| spellingShingle | Minjun Huang Xiaoli Li Xiaoyan Zheng Fei Wang Yang Zou Lei Wang PD-L2 Blockade Exacerbates Liver Lesion in Mice Infected with <i>Capillaria hepatica</i> through Reducing Alternatively Activated Macrophages Tropical Medicine and Infectious Disease alternatively activated macrophages <i>Capillaria hepatica</i> immunomodulation programmed death ligand 2 |
| title | PD-L2 Blockade Exacerbates Liver Lesion in Mice Infected with <i>Capillaria hepatica</i> through Reducing Alternatively Activated Macrophages |
| title_full | PD-L2 Blockade Exacerbates Liver Lesion in Mice Infected with <i>Capillaria hepatica</i> through Reducing Alternatively Activated Macrophages |
| title_fullStr | PD-L2 Blockade Exacerbates Liver Lesion in Mice Infected with <i>Capillaria hepatica</i> through Reducing Alternatively Activated Macrophages |
| title_full_unstemmed | PD-L2 Blockade Exacerbates Liver Lesion in Mice Infected with <i>Capillaria hepatica</i> through Reducing Alternatively Activated Macrophages |
| title_short | PD-L2 Blockade Exacerbates Liver Lesion in Mice Infected with <i>Capillaria hepatica</i> through Reducing Alternatively Activated Macrophages |
| title_sort | pd l2 blockade exacerbates liver lesion in mice infected with i capillaria hepatica i through reducing alternatively activated macrophages |
| topic | alternatively activated macrophages <i>Capillaria hepatica</i> immunomodulation programmed death ligand 2 |
| url | https://www.mdpi.com/2414-6366/8/1/46 |
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