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Article

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

by
Katrin Spekker-Bosker
1,†,
Christoph-Martin Ufermann
1,†,
Marco Maywald
2,3,
Albert Zimmermann
2,
Andreas Domröse
1,
Claudia Woite
1,
Walter Däubener
1 and
Silvia Kathrin Eller
1,*
1
Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany
2
Institute of Virology, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany
3
Bavarian Nordic GmbH, 82152 Martinsried, Germany
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(4), 858; https://doi.org/10.3390/ijms20040858
Submission received: 15 January 2019 / Revised: 5 February 2019 / Accepted: 12 February 2019 / Published: 16 February 2019
(This article belongs to the Special Issue Host-Cytomegalovirus Interactions: Pro- and Antiviral Key Factors Affecting CMV Infection Outcome or Therapeutic Approaches)
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Abstract

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.
Keywords: human cytomegalovirus; retinitis; uveitis; chorioretinitis; ocular toxoplasmosis; Indoleamine 2,3-dioxygenase-1; inducible nitric oxide synthase; Toxoplasma gondii; human retinal pigment epithelial cells; Staphylococcus aureus human cytomegalovirus; retinitis; uveitis; chorioretinitis; ocular toxoplasmosis; Indoleamine 2,3-dioxygenase-1; inducible nitric oxide synthase; Toxoplasma gondii; human retinal pigment epithelial cells; Staphylococcus aureus

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MDPI and ACS Style

Spekker-Bosker, K.; Ufermann, C.-M.; Maywald, M.; Zimmermann, A.; Domröse, A.; Woite, C.; Däubener, W.; Eller, S.K. hCMV-Mediated Immune Escape Mechanisms Favor Pathogen Growth and Disturb the Immune Privilege of the Eye. Int. J. Mol. Sci. 2019, 20, 858. https://doi.org/10.3390/ijms20040858

AMA Style

Spekker-Bosker K, Ufermann C-M, Maywald M, Zimmermann A, Domröse A, Woite C, Däubener W, Eller SK. hCMV-Mediated Immune Escape Mechanisms Favor Pathogen Growth and Disturb the Immune Privilege of the Eye. International Journal of Molecular Sciences. 2019; 20(4):858. https://doi.org/10.3390/ijms20040858

Chicago/Turabian Style

Spekker-Bosker, Katrin, Christoph-Martin Ufermann, Marco Maywald, Albert Zimmermann, Andreas Domröse, Claudia Woite, Walter Däubener, and Silvia Kathrin Eller. 2019. "hCMV-Mediated Immune Escape Mechanisms Favor Pathogen Growth and Disturb the Immune Privilege of the Eye" International Journal of Molecular Sciences 20, no. 4: 858. https://doi.org/10.3390/ijms20040858

APA Style

Spekker-Bosker, K., Ufermann, C.-M., Maywald, M., Zimmermann, A., Domröse, A., Woite, C., Däubener, W., & Eller, S. K. (2019). hCMV-Mediated Immune Escape Mechanisms Favor Pathogen Growth and Disturb the Immune Privilege of the Eye. International Journal of Molecular Sciences, 20(4), 858. https://doi.org/10.3390/ijms20040858

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