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hCMV-Mediated Immune Escape Mechanisms Favor Pathogen Growth and Disturb the Immune Privilege of the Eye

Human retinal pigment epithelial (hRPE) cells are important for the establishment and maintenance of the immune privilege of the eye. They function as target cells for human cytomegalovirus (hCMV), but are able to restrict viral replication. hCMV causes opportunistic posterior uveitis such as retini...

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Autores principales: Spekker-Bosker, Katrin, Ufermann, Christoph-Martin, Maywald, Marco, Zimmermann, Albert, Domröse, Andreas, Woite, Claudia, Däubener, Walter, Eller, Silvia Kathrin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413209/
https://www.ncbi.nlm.nih.gov/pubmed/30781494
http://dx.doi.org/10.3390/ijms20040858
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author Spekker-Bosker, Katrin
Ufermann, Christoph-Martin
Maywald, Marco
Zimmermann, Albert
Domröse, Andreas
Woite, Claudia
Däubener, Walter
Eller, Silvia Kathrin
author_facet Spekker-Bosker, Katrin
Ufermann, Christoph-Martin
Maywald, Marco
Zimmermann, Albert
Domröse, Andreas
Woite, Claudia
Däubener, Walter
Eller, Silvia Kathrin
author_sort Spekker-Bosker, Katrin
collection PubMed
description Human retinal pigment epithelial (hRPE) cells are important for the establishment and maintenance of the immune privilege of the eye. They function as target cells for human cytomegalovirus (hCMV), but are able to restrict viral replication. hCMV causes opportunistic posterior uveitis such as retinitis and chorioretinitis. Both mainly occur in severely immunocompromised patients and rarely manifest in immunocompetent individuals. In this study, hRPE cells were infected with hCMV in vitro and activated with proinflammatory cytokines. The enzymatic activities of indoleamine 2,3-dioxygenase-1 (IDO1) and inducible nitric oxide synthase (iNOS) were determined. The antimicrobial capacity of both molecules was analyzed in co-infection experiments using Staphylococcus aureus (S. aureus) and Toxoplasma gondii (T. gondii), causing uveitis in patients. We show that an hCMV infection of hRPE cells blocks IDO1 and iNOS mediated antimicrobial defense mechanisms necessary for the control of S. aureus and T. gondii. hCMV also inhibits immune suppressive effector mechanisms in hRPE. The interferon gamma-induced IDO1 dependent immune regulation was severely blocked, as detected by the loss of T cell inhibition. We conclude that an active hCMV infection in the eye might favor the replication of pathogens causing co-infections in immunosuppressed individuals. An hCMV caused blockade of IDO1 might weaken the eye’s immune privilege and favor the development of post-infectious autoimmune uveitis.
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spelling pubmed-64132092019-03-29 hCMV-Mediated Immune Escape Mechanisms Favor Pathogen Growth and Disturb the Immune Privilege of the Eye Spekker-Bosker, Katrin Ufermann, Christoph-Martin Maywald, Marco Zimmermann, Albert Domröse, Andreas Woite, Claudia Däubener, Walter Eller, Silvia Kathrin Int J Mol Sci Article Human retinal pigment epithelial (hRPE) cells are important for the establishment and maintenance of the immune privilege of the eye. They function as target cells for human cytomegalovirus (hCMV), but are able to restrict viral replication. hCMV causes opportunistic posterior uveitis such as retinitis and chorioretinitis. Both mainly occur in severely immunocompromised patients and rarely manifest in immunocompetent individuals. In this study, hRPE cells were infected with hCMV in vitro and activated with proinflammatory cytokines. The enzymatic activities of indoleamine 2,3-dioxygenase-1 (IDO1) and inducible nitric oxide synthase (iNOS) were determined. The antimicrobial capacity of both molecules was analyzed in co-infection experiments using Staphylococcus aureus (S. aureus) and Toxoplasma gondii (T. gondii), causing uveitis in patients. We show that an hCMV infection of hRPE cells blocks IDO1 and iNOS mediated antimicrobial defense mechanisms necessary for the control of S. aureus and T. gondii. hCMV also inhibits immune suppressive effector mechanisms in hRPE. The interferon gamma-induced IDO1 dependent immune regulation was severely blocked, as detected by the loss of T cell inhibition. We conclude that an active hCMV infection in the eye might favor the replication of pathogens causing co-infections in immunosuppressed individuals. An hCMV caused blockade of IDO1 might weaken the eye’s immune privilege and favor the development of post-infectious autoimmune uveitis. MDPI 2019-02-16 /pmc/articles/PMC6413209/ /pubmed/30781494 http://dx.doi.org/10.3390/ijms20040858 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Spekker-Bosker, Katrin
Ufermann, Christoph-Martin
Maywald, Marco
Zimmermann, Albert
Domröse, Andreas
Woite, Claudia
Däubener, Walter
Eller, Silvia Kathrin
hCMV-Mediated Immune Escape Mechanisms Favor Pathogen Growth and Disturb the Immune Privilege of the Eye
title hCMV-Mediated Immune Escape Mechanisms Favor Pathogen Growth and Disturb the Immune Privilege of the Eye
title_full hCMV-Mediated Immune Escape Mechanisms Favor Pathogen Growth and Disturb the Immune Privilege of the Eye
title_fullStr hCMV-Mediated Immune Escape Mechanisms Favor Pathogen Growth and Disturb the Immune Privilege of the Eye
title_full_unstemmed hCMV-Mediated Immune Escape Mechanisms Favor Pathogen Growth and Disturb the Immune Privilege of the Eye
title_short hCMV-Mediated Immune Escape Mechanisms Favor Pathogen Growth and Disturb the Immune Privilege of the Eye
title_sort hcmv-mediated immune escape mechanisms favor pathogen growth and disturb the immune privilege of the eye
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413209/
https://www.ncbi.nlm.nih.gov/pubmed/30781494
http://dx.doi.org/10.3390/ijms20040858
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