Dendritic Cell Autophagy Contributes to Herpes Simplex Virus-Driven Stromal Keratitis and Immunopathology

ABSTRACT Herpetic stromal keratitis (HSK) is a blinding ocular disease that is initiated by HSV-1 and characterized by chronic inflammation in the cornea. Although HSK immunopathology of the cornea is well documented in animal models, events preceding this abnormal inflammatory cascade are poorly un...

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Autores principales:	Yike Jiang, Xiaotang Yin, Patrick M. Stuart, David A. Leib
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7090509bce684d58bae0ced0291e0640
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spelling	oai:doaj.org-article:7090509bce684d58bae0ced0291e06402021-11-15T15:41:23ZDendritic Cell Autophagy Contributes to Herpes Simplex Virus-Driven Stromal Keratitis and Immunopathology10.1128/mBio.01426-152150-7511https://doaj.org/article/7090509bce684d58bae0ced0291e06402015-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01426-15https://doaj.org/toc/2150-7511ABSTRACT Herpetic stromal keratitis (HSK) is a blinding ocular disease that is initiated by HSV-1 and characterized by chronic inflammation in the cornea. Although HSK immunopathology of the cornea is well documented in animal models, events preceding this abnormal inflammatory cascade are poorly understood. In this study, we have examined the activation of pathological CD4+ T cells in the development of HSK. Dendritic cell autophagy (DC-autophagy) is an important pathway regulating major histocompatibility complex class II (MHCII)-dependent antigen presentation and proper CD4+ T cell activation during infectious diseases. Using DC-autophagy-deficient mice, we found that DC-autophagy significantly and specifically contributes to HSK disease without impacting early innate immune infiltration, viral clearance, or host survival. Instead, the observed phenotype was attributable to the abrogated activation of CD4+ T cells and reduced inflammation in HSK lesions. We conclude that DC-autophagy is an important contributor to primary HSK immunopathology upstream of CD4+ T cell activation. IMPORTANCE Herpetic stromal keratitis (HSK) is the leading cause of infectious blindness in the United States and a rising cause worldwide. HSK is induced by herpes simplex virus 1 but is considered a disease of inappropriately sustained inflammation driven by CD4+ T cells. In this study, we investigated whether pathways preceding CD4+ T cell activation affect disease outcome. We found that autophagy in dendritic cells significantly contributed to the incidence of HSK. Dendritic cell autophagy did not alter immune control of the virus or neurological disease but specifically augmented CD4+ T cell activation and pathological corneal inflammation. This study broadens our understanding of the immunopathology that drives HSK and implicates the autophagy pathway as a new target for therapeutic intervention against this incurable form of infectious blindness.Yike JiangXiaotang YinPatrick M. StuartDavid A. LeibAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 6 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Yike Jiang Xiaotang Yin Patrick M. Stuart David A. Leib Dendritic Cell Autophagy Contributes to Herpes Simplex Virus-Driven Stromal Keratitis and Immunopathology
description	ABSTRACT Herpetic stromal keratitis (HSK) is a blinding ocular disease that is initiated by HSV-1 and characterized by chronic inflammation in the cornea. Although HSK immunopathology of the cornea is well documented in animal models, events preceding this abnormal inflammatory cascade are poorly understood. In this study, we have examined the activation of pathological CD4+ T cells in the development of HSK. Dendritic cell autophagy (DC-autophagy) is an important pathway regulating major histocompatibility complex class II (MHCII)-dependent antigen presentation and proper CD4+ T cell activation during infectious diseases. Using DC-autophagy-deficient mice, we found that DC-autophagy significantly and specifically contributes to HSK disease without impacting early innate immune infiltration, viral clearance, or host survival. Instead, the observed phenotype was attributable to the abrogated activation of CD4+ T cells and reduced inflammation in HSK lesions. We conclude that DC-autophagy is an important contributor to primary HSK immunopathology upstream of CD4+ T cell activation. IMPORTANCE Herpetic stromal keratitis (HSK) is the leading cause of infectious blindness in the United States and a rising cause worldwide. HSK is induced by herpes simplex virus 1 but is considered a disease of inappropriately sustained inflammation driven by CD4+ T cells. In this study, we investigated whether pathways preceding CD4+ T cell activation affect disease outcome. We found that autophagy in dendritic cells significantly contributed to the incidence of HSK. Dendritic cell autophagy did not alter immune control of the virus or neurological disease but specifically augmented CD4+ T cell activation and pathological corneal inflammation. This study broadens our understanding of the immunopathology that drives HSK and implicates the autophagy pathway as a new target for therapeutic intervention against this incurable form of infectious blindness.
format	article
author	Yike Jiang Xiaotang Yin Patrick M. Stuart David A. Leib
author_facet	Yike Jiang Xiaotang Yin Patrick M. Stuart David A. Leib
author_sort	Yike Jiang
title	Dendritic Cell Autophagy Contributes to Herpes Simplex Virus-Driven Stromal Keratitis and Immunopathology
title_short	Dendritic Cell Autophagy Contributes to Herpes Simplex Virus-Driven Stromal Keratitis and Immunopathology
title_full	Dendritic Cell Autophagy Contributes to Herpes Simplex Virus-Driven Stromal Keratitis and Immunopathology
title_fullStr	Dendritic Cell Autophagy Contributes to Herpes Simplex Virus-Driven Stromal Keratitis and Immunopathology
title_full_unstemmed	Dendritic Cell Autophagy Contributes to Herpes Simplex Virus-Driven Stromal Keratitis and Immunopathology
title_sort	dendritic cell autophagy contributes to herpes simplex virus-driven stromal keratitis and immunopathology
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/7090509bce684d58bae0ced0291e0640
work_keys_str_mv	AT yikejiang dendriticcellautophagycontributestoherpessimplexvirusdrivenstromalkeratitisandimmunopathology AT xiaotangyin dendriticcellautophagycontributestoherpessimplexvirusdrivenstromalkeratitisandimmunopathology AT patrickmstuart dendriticcellautophagycontributestoherpessimplexvirusdrivenstromalkeratitisandimmunopathology AT davidaleib dendriticcellautophagycontributestoherpessimplexvirusdrivenstromalkeratitisandimmunopathology
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Dendritic Cell Autophagy Contributes to Herpes Simplex Virus-Driven Stromal Keratitis and Immunopathology

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