Oligoadenylate Synthetase/Protein Kinase R Pathways and αβ TCR+ T Cells Are Required for Adenovirus Vector: IFN-γ Inhibition of Herpes Simplex Virus-1 in Cornea

Austin, Bobbie Ann; Halford, William P.; Williams, Bryan R.G.; Carr, Daniel J.J.

doi:10.4049/jimmunol.178.8.5166

Cited by 10 publications

(12 citation statements)

References 73 publications

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“…We found a significant increase in gene expression of IFN-γ in the cornea of rabbits treated for seven days. Early studies have shown that IFN-γ has a protective effect during infection (Austin et al, 2007; He et al, 1999; Minami et al, 2002). It has been reported that in mice, IFN-γ reduces replication of the HSV-1 virus in the TG by a mechanism that involves CD8+T cells and reduction of infected early protein 0 (ICP0) expression.…”

Section: Discussionmentioning

confidence: 99%

PEDF plus DHA modulate inflammation and stimulate nerve regeneration after HSV-1 infection

Neumann

Kakazu

et al. 2017

Experimental Eye Research

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Herpes simplex virus type-1 (HSV-1) infection leads to impaired corneal sensation and, in severe cases, to corneal ulceration, melting and perforation. Here, we explore the potential therapeutic action of pigment epithelial-derived factor (PEDF) plus docosahexaenoic acid (DHA) on corneal inflammation and nerve regeneration following HSV-1 infection. Rabbits inoculated with 100,000 PFU/eye of HSV-1 strain 17Syn+ were treated with PEDF+DHA or vehicle. PEDF+DHA treatment resulted in a biphasic immune response with stronger infiltration of CD4+T cells, neutrophils and macrophages at 7-days post-treatment (p.t.) that was significantly decreased by 14 days, compared to the vehicle-treated group. Screening of 14 immune-related genes by q-PCR showed that treatment induced higher expression of IFN-γ and CCL20 and inhibition of IL-18 by 7 days in the cornea. PEDF+DHA-treated animals developed less dendritic corneal lesions, opacity and neovascularization. Corneal nerve density increased at 12-weeks p.t. with functional recovery of corneal sensation. Treatment with PEDF+DHA that was postponed by 3 weeks also showed increased nerve density when compared to vehicle. Our data demonstrate that PEDF+DHA promotes resolution of the inflammatory response to the virus and, most importantly, induces regeneration of damaged corneal nerves vital for maintaining ocular surface homeostasis.

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Section: Discussionmentioning

confidence: 99%

PEDF plus DHA modulate inflammation and stimulate nerve regeneration after HSV-1 infection

Neumann

Kakazu

et al. 2017

Experimental Eye Research

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“…Plaques were visualized and enumerated with the aid of an inverted microscope 24 to 48 hours later and quantified as mean log plaque-forming units per pair of corneas or per cornea, as previously described. 27 …”

Section: Viral Plaque Assaymentioning

confidence: 99%

IL-6 Contributes to Corneal Nerve Degeneration after Herpes Simplex Virus Type I Infection

Chucair-Elliott

Jinkins

Carr

et al. 2016

The American Journal of Pathology

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Herpes simplex virus type 1 (HSV-1) is a leading cause of neurotrophic keratitis characterized by decreased corneal sensation because of damage to the corneal sensory fibers. We and others have reported regression of corneal nerves during acute HSV-1 infection. To determine whether denervation is caused directly by the virus or indirectly by the elicited immune response, mice were infected with HSV-1 and topically treated with dexamethasone (DEX) or control eye drops. Corneal sensitivity was measured using a Cochet-Bonnet esthesiometer and nerve network structure via immunohistochemistry. Corneas were assessed for viral content by plaque assay, leukocyte influx by flow cytometry, and content of chemokines and inflammatory cytokines by suspension array. DEX significantly preserved corneal nerve structure and sensitivity on infection. DEX reduced myeloid and T-cell populations in the cornea and did not affect viral contents at 4 and 8 days post infection. The elevated protein contents of chemokines and inflammatory cytokines on infection were greatly suppressed by DEX. Subconjunctival delivery of neutralizing antibody against IL-6 to infected mice resulted in partial preservation of corneal nerve structure and sensitivity. Our study supports a role for the immune response, but not local virus replication in the development of HSV-1einduced neurotrophic keratitis. IL-6 is one of the factors produced by the elicited inflammatory response to HSV-1 infection contributing to nerve regression.

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“…by plaque assay as previously described. 18 P. aeruginosa levels were determined in the designated tissues at indicated times p.i. following homogenization of tissue in sterile PBS and plating of serially diluted sample on agar plates.…”

Section: Corneal Infectionmentioning

confidence: 99%

CXCL1-Deficient Mice Are Highly Sensitive toPseudomonas aeruginosabut Not Herpes Simplex Virus Type 1 Corneal Infection

Bryant-Hudson

Carr²

2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To determine the role of the chemokine CXCL1 on leukocyte recruitment, cytokine production and host resistance during HSV-1 and Pseudomonas aeruginosa infection.METHODS. Viral titer and bacterial load were compared following infection of wild-type (WT) and CXCL1 À/À mice. Corneal leukocyte recruitment was determined using flow cytometry. Cytokine levels were assessed by luminex-based suspension arrays. Hematoxylin and eosin (H&E) staining, confocal microscopy, and optical coherence tomography (OCT) were used to visualize leukocyte recruitment and corneal thickening. RESULTS. HSV-1-infected WT and CXCL1À/À mice possessed similar viral titers in the cornea during late acute infection. Flow cytometry analysis detected similar leukocyte levels in the cornea following infection as well. By comparison, there was a significant increase in P. aeruginosa recovered from CXCL1 À/À corneas as compared with WT mice. Imaging analysis and histochemical staining revealed impaired leukocyte recruitment to the central cornea and earlier corneal thickening in CXCL1 À/À mice. IFN-c, CCL2, and CCL5 protein levels were similar between WT and CXCL1 À/À corneas following HSV-1 or P. aeruginosa infection. However, CXCL2 levels were significantly reduced in the CXCL1 À/À corneas following either infection.CONCLUSIONS. The absence of CXCL1 and CXCL2 expression significantly impairs the ability of the host to control P. aeruginosa replication through the recruitment of leukocytes to the central cornea. In contrast, CXCL1, CXCL2, and the cells they recruit, are not required for HSV-1 clearance during acute infection. (Invest Ophthalmol Vis Sci. 2012;53:6785-6792)

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Oligoadenylate Synthetase/Protein Kinase R Pathways and αβ TCR+ T Cells Are Required for Adenovirus Vector: IFN-γ Inhibition of Herpes Simplex Virus-1 in Cornea

Cited by 10 publications

References 73 publications

PEDF plus DHA modulate inflammation and stimulate nerve regeneration after HSV-1 infection

PEDF plus DHA modulate inflammation and stimulate nerve regeneration after HSV-1 infection

IL-6 Contributes to Corneal Nerve Degeneration after Herpes Simplex Virus Type I Infection

CXCL1-Deficient Mice Are Highly Sensitive toPseudomonas aeruginosabut Not Herpes Simplex Virus Type 1 Corneal Infection

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