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Indoleamine 2,3-Dioxygenase Regulates Macrophage Recruitment, Polarization and Phagocytosis in Aspergillus Fumigatus Keratitis
PURPOSE: To explore the influence of indoleamine 2,3-dioxygenase (IDO) on macrophage recruitment, polarization and phagocytosis in Aspergillus fumigatus keratitis. METHODS: A murine model of A. fumigatus keratitis and peritoneal macrophages incubated with the hyphae of A. fumigatus were used. Macrop...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Association for Research in Vision and Ophthalmology
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425693/ https://www.ncbi.nlm.nih.gov/pubmed/32692841 http://dx.doi.org/10.1167/iovs.61.8.28 |
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author | Jiang, Nan Zhang, Li Zhao, Guiqiu Lin, Jing Wang, Qian Xu, Qiang Li, Cui Hu, Liting Peng, Xudong Yu, Feifei Xu, Ming |
author_facet | Jiang, Nan Zhang, Li Zhao, Guiqiu Lin, Jing Wang, Qian Xu, Qiang Li, Cui Hu, Liting Peng, Xudong Yu, Feifei Xu, Ming |
author_sort | Jiang, Nan |
collection | PubMed |
description | PURPOSE: To explore the influence of indoleamine 2,3-dioxygenase (IDO) on macrophage recruitment, polarization and phagocytosis in Aspergillus fumigatus keratitis. METHODS: A murine model of A. fumigatus keratitis and peritoneal macrophages incubated with the hyphae of A. fumigatus were used. Macrophage recruitment in corneas was evaluated using immunofluorescence staining. The polarization of macrophages, which was stimulated by A. fumigatus and pretreatment with or without 1-methyltryptophan (1-MT), interferon gamma (IFNG), extracellular regulated protein kinases (ERK) antagonist, and p38 antagonist, was determined using reverse-transcription polymerase chain reaction and flow cytometry. P38 and ERK levels were determined using Western blotting. Macrophage phagocytosis was examined using colony-forming units. RESULTS: Compared with the A.F. group, recruitment of macrophages increased, tumor necrosis factor–α (TNF-α) and inducible nitric oxide synthase (iNOS) expression decreased, whereas arginase-1 (Arg-1) and interleukin-10 (IL-10) expression increased in the mouse corneas of the 1-MT+A.F. group. The ratio of CD206(+)/CD86(+) macrophages in the corneas and spleens of 1-MT+A.F. group increased. Furthermore, in peritoneal macrophages stimulated by A. fumigatus, 1-MT promoted Arg-1 and IL-10 expression while upregulating the ratio of CD206(+)/CD86(+) macrophages. Conversely, IDO agonist IFNG promoted TNF-α and iNOS expression, inhibited Arg-1 and IL-10 expression and downregulated the ratio of CD206(+)/CD86(+) macrophages. The role of IFNG was reversed by the antagonist of P38 or ERK. P38 and ERK levels were downregulated in corneas of 1-MT+A.F. group. Besides, IFNG inhibited macrophage phagocytosis. CONCLUSIONS: IDO inhibited macrophage recruitment and phagocytosis in A. fumigatus keratitis. Mechanistically, IDO is involved in M1 macrophage polarization in A. fumigatus keratitis through a MAPK/ERK-dependent pathway. |
format | Online Article Text |
id | pubmed-7425693 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Association for Research in Vision and Ophthalmology |
record_format | MEDLINE/PubMed |
spelling | pubmed-74256932020-08-26 Indoleamine 2,3-Dioxygenase Regulates Macrophage Recruitment, Polarization and Phagocytosis in Aspergillus Fumigatus Keratitis Jiang, Nan Zhang, Li Zhao, Guiqiu Lin, Jing Wang, Qian Xu, Qiang Li, Cui Hu, Liting Peng, Xudong Yu, Feifei Xu, Ming Invest Ophthalmol Vis Sci Cornea PURPOSE: To explore the influence of indoleamine 2,3-dioxygenase (IDO) on macrophage recruitment, polarization and phagocytosis in Aspergillus fumigatus keratitis. METHODS: A murine model of A. fumigatus keratitis and peritoneal macrophages incubated with the hyphae of A. fumigatus were used. Macrophage recruitment in corneas was evaluated using immunofluorescence staining. The polarization of macrophages, which was stimulated by A. fumigatus and pretreatment with or without 1-methyltryptophan (1-MT), interferon gamma (IFNG), extracellular regulated protein kinases (ERK) antagonist, and p38 antagonist, was determined using reverse-transcription polymerase chain reaction and flow cytometry. P38 and ERK levels were determined using Western blotting. Macrophage phagocytosis was examined using colony-forming units. RESULTS: Compared with the A.F. group, recruitment of macrophages increased, tumor necrosis factor–α (TNF-α) and inducible nitric oxide synthase (iNOS) expression decreased, whereas arginase-1 (Arg-1) and interleukin-10 (IL-10) expression increased in the mouse corneas of the 1-MT+A.F. group. The ratio of CD206(+)/CD86(+) macrophages in the corneas and spleens of 1-MT+A.F. group increased. Furthermore, in peritoneal macrophages stimulated by A. fumigatus, 1-MT promoted Arg-1 and IL-10 expression while upregulating the ratio of CD206(+)/CD86(+) macrophages. Conversely, IDO agonist IFNG promoted TNF-α and iNOS expression, inhibited Arg-1 and IL-10 expression and downregulated the ratio of CD206(+)/CD86(+) macrophages. The role of IFNG was reversed by the antagonist of P38 or ERK. P38 and ERK levels were downregulated in corneas of 1-MT+A.F. group. Besides, IFNG inhibited macrophage phagocytosis. CONCLUSIONS: IDO inhibited macrophage recruitment and phagocytosis in A. fumigatus keratitis. Mechanistically, IDO is involved in M1 macrophage polarization in A. fumigatus keratitis through a MAPK/ERK-dependent pathway. The Association for Research in Vision and Ophthalmology 2020-07-21 /pmc/articles/PMC7425693/ /pubmed/32692841 http://dx.doi.org/10.1167/iovs.61.8.28 Text en Copyright 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. |
spellingShingle | Cornea Jiang, Nan Zhang, Li Zhao, Guiqiu Lin, Jing Wang, Qian Xu, Qiang Li, Cui Hu, Liting Peng, Xudong Yu, Feifei Xu, Ming Indoleamine 2,3-Dioxygenase Regulates Macrophage Recruitment, Polarization and Phagocytosis in Aspergillus Fumigatus Keratitis |
title | Indoleamine 2,3-Dioxygenase Regulates Macrophage Recruitment, Polarization and Phagocytosis in Aspergillus Fumigatus Keratitis |
title_full | Indoleamine 2,3-Dioxygenase Regulates Macrophage Recruitment, Polarization and Phagocytosis in Aspergillus Fumigatus Keratitis |
title_fullStr | Indoleamine 2,3-Dioxygenase Regulates Macrophage Recruitment, Polarization and Phagocytosis in Aspergillus Fumigatus Keratitis |
title_full_unstemmed | Indoleamine 2,3-Dioxygenase Regulates Macrophage Recruitment, Polarization and Phagocytosis in Aspergillus Fumigatus Keratitis |
title_short | Indoleamine 2,3-Dioxygenase Regulates Macrophage Recruitment, Polarization and Phagocytosis in Aspergillus Fumigatus Keratitis |
title_sort | indoleamine 2,3-dioxygenase regulates macrophage recruitment, polarization and phagocytosis in aspergillus fumigatus keratitis |
topic | Cornea |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425693/ https://www.ncbi.nlm.nih.gov/pubmed/32692841 http://dx.doi.org/10.1167/iovs.61.8.28 |
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