Role of T<sub>H</sub>17 Responses in Increasing Herpetic Keratitis in the Eyes of Mice Infected with HSV-1

Hirose, Sachiko; Jaggi, Ujjaldeep; Wang, Shaohui; Tormanen, Kati; Nagaoka, Yoshiko; Katsumata, Makoto; Ghiasi, Homayon

doi:10.1167/iovs.61.6.20

Cited by 5 publications

(4 citation statements)

References 115 publications

(187 reference statements)

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“…Since IL-17A binds to both IL-17RA and IL-17RC, detection of demyelination in IL-17RA -/- and IL-17RC -/- mice may suggest that the other receptor compensates for the missing receptor for binding to IL-17A. Thus, to determine if the absence of both RA and RC molecules is required to block CNS demyelination in infected mice, we generated mice lacking a combination of both IL-17RA and IL-17RC as we described previously ( 41 ). We infected IL-17RA -/- RC -/- mice with HSV-IL-2 and looked for demyelination in optic nerve, brain, and spinal cord sections of infected mice as above.…”

Section: Resultsmentioning

confidence: 99%

“…IL-17RC -/- mice were developed by Genentech and were obtained from the Mutant Mouse Regional Resource Center (University of California, Davis). IL-17RA -/- and IL-17RA -/- RC -/- were developed in our Lab and described previously ( 41 ). IL-17RD -/- mice were obtained from the Mutant Mouse Regional Resource Center (University of California, Davis).…”

Section: Methodsmentioning

confidence: 99%

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IL-17A expression by both T cells and non-T cells contribute to HSV-IL-2-induced CNS demyelination

Hirose

Wang²,

Jaggi³

et al. 2023

Front. Immunol.

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Previously we reported that a recombinant HSV-1 expressing murine IL-2 (HSV-IL-2) causes CNS demyelination in different strains of mice and in a T cell-dependent manner. Since TH17 cells have been implicated in CNS pathology, in the present study, we looked into the effects of IL-17A-/- and three of its receptors on HSV-IL-2-induced CNS demyelination. IL-17A-/- mice did not develop CNS demyelination, while IL-17RA-/-, IL-17RC-/-, IL-17RD-/- and IL-17RA-/-RC-/- mice developed CNS demyelination. Adoptive transfer of T cells from wild-type (WT) mice to IL-17A-/- mice or T cells from IL-17A-/- mice to Rag-/- mice induced CNS demyelination in infected mice. Adoptive T cell experiments suggest that both T cells and non-T cells expressing IL-17A contribute to HSV-IL-2-induced CNS demyelination with no difference in the severity of demyelination between the two groups of IL-17A producing cells. IL-6, IL-10, or TGFβ did not contribute to CNS demyelination in infected mice. Transcriptome analysis between IL-17A-/- brain and spinal cord of infected mice with and without T cell transfer from WT mice revealed that “neuron projection extension involved in neuron projection guidance” and “ensheathment of neurons” pathways were associated with CNS demyelination. Collectively, the results indicate the importance of IL-17A in CNS demyelination and the possible involvement of more than three of IL-17 receptors in CNS demyelination.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

IL-17A expression by both T cells and non-T cells contribute to HSV-IL-2-induced CNS demyelination

Hirose

Wang²,

Jaggi³

et al. 2023

Front. Immunol.

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“…This may be due to its selective autophagy regulatory properties. Hirose et al [ 200 ] investigated the role of TH17 responses in an HSV-1-infected murine model and concluded that interleukin-17 protects against ocular morbidity secondary to HSV-1[ 200 ].…”

Section: Immune Responses In Herpes Simplex Keratitis: Implications F...mentioning

confidence: 99%

Herpes simplex keratitis: A brief clinical overview

Musa,

Enaholo,

Aluyi-Osa

et al. 2024

World J Virol

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The aim of our minireview is to provide a brief overview of the diagnosis, clinical aspects, treatment options, management, and current literature available regarding herpes simplex keratitis (HSK). This type of corneal viral infection is caused by the herpes simplex virus (HSV), which can affect several tissues, including the cornea. One significant aspect of HSK is its potential to cause recurrent episodes of inflammation and damage to the cornea. After the initial infection, the HSV can establish a latent infection in the trigeminal ganglion, a nerve cluster near the eye. The virus may remain dormant for extended periods. Periodic reactivation of the virus can occur, leading to recurrent episodes of HSK. Factors triggering reactivation include stress, illness, immunosuppression, or trauma. Recurrent episodes can manifest in different clinical patterns, ranging from mild epithelial involvement to more severe stromal or endothelial disease. The severity and frequency of recurrences vary among individuals. Severe cases of HSK, especially those involving the stroma and leading to scarring, can result in vision impairment or even blindness in extreme cases. The cornea's clarity is crucial for good vision, and scarring can compromise this, potentially leading to visual impairment. The management of HSK involves not only treating acute episodes but also implementing long-term strategies to prevent recurrences and attempt repairs of corneal nerve endings via neurotization. Antiviral medications, such as oral Acyclovir or topical Ganciclovir, may be prescribed for prophylaxis. The immune response to the virus can contribute to corneal damage. Inflammation, caused by the body's attempt to control the infection, may inadvertently harm the corneal tissues. Clinicians should be informed about triggers and advised on measures to minimize the risk of reactivation. In summary, the recurrent nature of HSK underscores the importance of both acute and long-term management strategies to preserve corneal health and maintain optimal visual function.

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“…Similarly, IL17RD (P10) also regulates JNK signaling and TLR signaling (Girondel and Meloche, 2021). Additionally the IL17 receptor has been ascribed a role in HSV-1 infection (Hirose et al, 2020). FLT1 (P14) activates the MAPK signaling pathway and its expression is increased in HSV-infected sensory neurons (Kramer et al, 2003).…”

Section: Variants In Innate and Adaptive Signaling Pathwaysmentioning

confidence: 99%

Whole exome sequencing of patients with varicella-zoster virus and herpes simplex virus induced acute retinal necrosis reveals rare disease-associated genetic variants

Heinz,

Swagemakers,

von Hofsten

et al. 2023

Front. Mol. Neurosci.

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PurposeHerpes simplex virus (HSV) and varicella-zoster virus (VZV) are neurotropic human alphaherpesviruses endemic worldwide. Upon primary infection, both viruses establish lifelong latency in neurons and reactivate intermittently to cause a variety of mild to severe diseases. Acute retinal necrosis (ARN) is a rare, sight-threatening eye disease induced by ocular VZV or HSV infection. The virus and host factors involved in ARN pathogenesis remain incompletely described. We hypothesize an underlying genetic defect in at least part of ARN cases.MethodsWe collected blood from 17 patients with HSV-or VZV-induced ARN, isolated DNA and performed Whole Exome Sequencing by Illumina followed by analysis in Varseq with criteria of CADD score > 15 and frequency in GnomAD < 0.1% combined with biological filters. Gene modifications relative to healthy control genomes were filtered according to high quality and read-depth, low frequency, high deleteriousness predictions and biological relevance.ResultsWe identified a total of 50 potentially disease-causing genetic variants, including missense, frameshift and splice site variants and on in-frame deletion in 16 of the 17 patients. The vast majority of these genes are involved in innate immunity, followed by adaptive immunity, autophagy, and apoptosis; in several instances variants within a given gene or pathway was identified in several patients.DiscussionWe propose that the identified variants may contribute to insufficient viral control and increased necrosis ocular disease presentation in the patients and serve as a knowledge base and starting point for the development of improved diagnostic, prophylactic, and therapeutic applications.

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Role of T_H17 Responses in Increasing Herpetic Keratitis in the Eyes of Mice Infected with HSV-1

Cited by 5 publications

References 115 publications

IL-17A expression by both T cells and non-T cells contribute to HSV-IL-2-induced CNS demyelination

IL-17A expression by both T cells and non-T cells contribute to HSV-IL-2-induced CNS demyelination

Herpes simplex keratitis: A brief clinical overview

Whole exome sequencing of patients with varicella-zoster virus and herpes simplex virus induced acute retinal necrosis reveals rare disease-associated genetic variants

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Role of TH17 Responses in Increasing Herpetic Keratitis in the Eyes of Mice Infected with HSV-1

Cited by 5 publications

References 115 publications

IL-17A expression by both T cells and non-T cells contribute to HSV-IL-2-induced CNS demyelination

IL-17A expression by both T cells and non-T cells contribute to HSV-IL-2-induced CNS demyelination

Herpes simplex keratitis: A brief clinical overview

Whole exome sequencing of patients with varicella-zoster virus and herpes simplex virus induced acute retinal necrosis reveals rare disease-associated genetic variants

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Product

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Role of T_H17 Responses in Increasing Herpetic Keratitis in the Eyes of Mice Infected with HSV-1