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PD-L2 Blockade Exacerbates Liver Lesion in Mice Infected with Capillaria hepatica through Reducing Alternatively Activated Macrophages

Capillaria hepatica 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 C. hepatica are not fully understood, and the role(s) of the programmed death 1 (PD-1) signaling pathway...

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Autores principales: Huang, Minjun, Li, Xiaoli, Zheng, Xiaoyan, Wang, Fei, Zou, Yang, Wang, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9866821/
https://www.ncbi.nlm.nih.gov/pubmed/36668953
http://dx.doi.org/10.3390/tropicalmed8010046
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author Huang, Minjun
Li, Xiaoli
Zheng, Xiaoyan
Wang, Fei
Zou, Yang
Wang, Lei
author_facet Huang, Minjun
Li, Xiaoli
Zheng, Xiaoyan
Wang, Fei
Zou, Yang
Wang, Lei
author_sort Huang, Minjun
collection PubMed
description Capillaria hepatica 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 C. hepatica are not fully understood, and the role(s) of the programmed death 1 (PD-1) signaling pathway in the context of C. hepatica-induced pathology are not known. In this study, we identify that the late stage of infection with C. hepatica—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.
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spelling pubmed-98668212023-01-22 PD-L2 Blockade Exacerbates Liver Lesion in Mice Infected with Capillaria hepatica through Reducing Alternatively Activated Macrophages Huang, Minjun Li, Xiaoli Zheng, Xiaoyan Wang, Fei Zou, Yang Wang, Lei Trop Med Infect Dis Article Capillaria hepatica 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 C. hepatica are not fully understood, and the role(s) of the programmed death 1 (PD-1) signaling pathway in the context of C. hepatica-induced pathology are not known. In this study, we identify that the late stage of infection with C. hepatica—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. MDPI 2023-01-06 /pmc/articles/PMC9866821/ /pubmed/36668953 http://dx.doi.org/10.3390/tropicalmed8010046 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huang, Minjun
Li, Xiaoli
Zheng, Xiaoyan
Wang, Fei
Zou, Yang
Wang, Lei
PD-L2 Blockade Exacerbates Liver Lesion in Mice Infected with Capillaria hepatica through Reducing Alternatively Activated Macrophages
title PD-L2 Blockade Exacerbates Liver Lesion in Mice Infected with Capillaria hepatica through Reducing Alternatively Activated Macrophages
title_full PD-L2 Blockade Exacerbates Liver Lesion in Mice Infected with Capillaria hepatica through Reducing Alternatively Activated Macrophages
title_fullStr PD-L2 Blockade Exacerbates Liver Lesion in Mice Infected with Capillaria hepatica through Reducing Alternatively Activated Macrophages
title_full_unstemmed PD-L2 Blockade Exacerbates Liver Lesion in Mice Infected with Capillaria hepatica through Reducing Alternatively Activated Macrophages
title_short PD-L2 Blockade Exacerbates Liver Lesion in Mice Infected with Capillaria hepatica through Reducing Alternatively Activated Macrophages
title_sort pd-l2 blockade exacerbates liver lesion in mice infected with capillaria hepatica through reducing alternatively activated macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9866821/
https://www.ncbi.nlm.nih.gov/pubmed/36668953
http://dx.doi.org/10.3390/tropicalmed8010046
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