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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...

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Autores principales: Jiang, Nan, Zhang, Li, Zhao, Guiqiu, Lin, Jing, Wang, Qian, Xu, Qiang, Li, Cui, Hu, Liting, Peng, Xudong, Yu, Feifei, Xu, Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2020
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.
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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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