Intramuscular Vaccination With the HSV-1(VC2) Live-Attenuated Vaccine Strain Confers Protection Against Viral Ocular Immunopathogenesis Associated With γδT Cell Intracorneal Infiltration

Herpes simplex virus type-1 (HSV-1) ocular infection is one of the leading causes of infectious blindness in developed countries. The resultant herpetic keratitis (HK) is caused by an exacerbated reaction of the adaptive immune response that persists beyond virus clearance causing substantial damage...

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Autores principales:	Rafiq Nabi, Andrew C. Lewin, Therese M. Collantes, Vladimir N. Chouljenko, Konstantin G. Kousoulas
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	herpes simplex gamma delta T cells immunopathogenesis ocular infection herpes keratitis Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/542e6ab357ea4ab496a603d4745905a1
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spelling	oai:doaj.org-article:542e6ab357ea4ab496a603d4745905a12021-11-15T05:43:21ZIntramuscular Vaccination With the HSV-1(VC2) Live-Attenuated Vaccine Strain Confers Protection Against Viral Ocular Immunopathogenesis Associated With γδT Cell Intracorneal Infiltration1664-322410.3389/fimmu.2021.789454https://doaj.org/article/542e6ab357ea4ab496a603d4745905a12021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.789454/fullhttps://doaj.org/toc/1664-3224Herpes simplex virus type-1 (HSV-1) ocular infection is one of the leading causes of infectious blindness in developed countries. The resultant herpetic keratitis (HK) is caused by an exacerbated reaction of the adaptive immune response that persists beyond virus clearance causing substantial damage to the cornea. Intramuscular immunization of mice with the HSV-1(VC2) live-attenuated vaccine strain has been shown to protect mice against lethal ocular challenge. Herein, we show that following ocular challenge, VC2 vaccinated animals control ocular immunopathogenesis in the absence of neutralizing antibodies on ocular surfaces. Ocular protection is associated with enhanced intracorneal infiltration of γδ T cells compared to mock-vaccinated animals. The observed γδ T cellular infiltration was inversely proportional to the infiltration of neutrophils, the latter associated with exacerbated tissue damage. Inhibition of T cell migration into ocular tissues by the S1P receptors agonist FTY720 produced significant ocular disease in vaccinated mice and marked increase in neutrophil infiltration. These results indicate that ocular challenge of mice immunized with the VC2 vaccine induce a unique ocular mucosal response that leads into the infiltration of γδ T cells resulting in the amelioration of infection-associated immunopathogenesis.Rafiq NabiAndrew C. LewinTherese M. CollantesVladimir N. ChouljenkoKonstantin G. KousoulasFrontiers Media S.A.articleherpes simplexgamma delta T cellsimmunopathogenesisocular infectionherpes keratitisImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	herpes simplex gamma delta T cells immunopathogenesis ocular infection herpes keratitis Immunologic diseases. Allergy RC581-607
spellingShingle	herpes simplex gamma delta T cells immunopathogenesis ocular infection herpes keratitis Immunologic diseases. Allergy RC581-607 Rafiq Nabi Andrew C. Lewin Therese M. Collantes Vladimir N. Chouljenko Konstantin G. Kousoulas Intramuscular Vaccination With the HSV-1(VC2) Live-Attenuated Vaccine Strain Confers Protection Against Viral Ocular Immunopathogenesis Associated With γδT Cell Intracorneal Infiltration
description	Herpes simplex virus type-1 (HSV-1) ocular infection is one of the leading causes of infectious blindness in developed countries. The resultant herpetic keratitis (HK) is caused by an exacerbated reaction of the adaptive immune response that persists beyond virus clearance causing substantial damage to the cornea. Intramuscular immunization of mice with the HSV-1(VC2) live-attenuated vaccine strain has been shown to protect mice against lethal ocular challenge. Herein, we show that following ocular challenge, VC2 vaccinated animals control ocular immunopathogenesis in the absence of neutralizing antibodies on ocular surfaces. Ocular protection is associated with enhanced intracorneal infiltration of γδ T cells compared to mock-vaccinated animals. The observed γδ T cellular infiltration was inversely proportional to the infiltration of neutrophils, the latter associated with exacerbated tissue damage. Inhibition of T cell migration into ocular tissues by the S1P receptors agonist FTY720 produced significant ocular disease in vaccinated mice and marked increase in neutrophil infiltration. These results indicate that ocular challenge of mice immunized with the VC2 vaccine induce a unique ocular mucosal response that leads into the infiltration of γδ T cells resulting in the amelioration of infection-associated immunopathogenesis.
format	article
author	Rafiq Nabi Andrew C. Lewin Therese M. Collantes Vladimir N. Chouljenko Konstantin G. Kousoulas
author_facet	Rafiq Nabi Andrew C. Lewin Therese M. Collantes Vladimir N. Chouljenko Konstantin G. Kousoulas
author_sort	Rafiq Nabi
title	Intramuscular Vaccination With the HSV-1(VC2) Live-Attenuated Vaccine Strain Confers Protection Against Viral Ocular Immunopathogenesis Associated With γδT Cell Intracorneal Infiltration
title_short	Intramuscular Vaccination With the HSV-1(VC2) Live-Attenuated Vaccine Strain Confers Protection Against Viral Ocular Immunopathogenesis Associated With γδT Cell Intracorneal Infiltration
title_full	Intramuscular Vaccination With the HSV-1(VC2) Live-Attenuated Vaccine Strain Confers Protection Against Viral Ocular Immunopathogenesis Associated With γδT Cell Intracorneal Infiltration
title_fullStr	Intramuscular Vaccination With the HSV-1(VC2) Live-Attenuated Vaccine Strain Confers Protection Against Viral Ocular Immunopathogenesis Associated With γδT Cell Intracorneal Infiltration
title_full_unstemmed	Intramuscular Vaccination With the HSV-1(VC2) Live-Attenuated Vaccine Strain Confers Protection Against Viral Ocular Immunopathogenesis Associated With γδT Cell Intracorneal Infiltration
title_sort	intramuscular vaccination with the hsv-1(vc2) live-attenuated vaccine strain confers protection against viral ocular immunopathogenesis associated with γδt cell intracorneal infiltration
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/542e6ab357ea4ab496a603d4745905a1
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Intramuscular Vaccination With the HSV-1(VC2) Live-Attenuated Vaccine Strain Confers Protection Against Viral Ocular Immunopathogenesis Associated With γδT Cell Intracorneal Infiltration

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