An intact complement system dampens cornea inflammation during acute primary HSV-1 infection

Abstract Corneal transparency is an essential characteristic necessary for normal vision. In response to microbial infection, the integrity of the cornea can become compromised as a result of the inflammatory response and the ensuing tissue pathology including neovascularization (NV) and collagen la...

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Main Authors: Adrian Filiberti, Grzegorz B. Gmyrek, Amanda N. Berube, Derek J. Royer, Daniel J. J. Carr
Format: Article
Language:English
Published: Nature Portfolio 2021-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-89818-9
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author Adrian Filiberti
Grzegorz B. Gmyrek
Amanda N. Berube
Derek J. Royer
Daniel J. J. Carr
author_facet Adrian Filiberti
Grzegorz B. Gmyrek
Amanda N. Berube
Derek J. Royer
Daniel J. J. Carr
author_sort Adrian Filiberti
collection DOAJ
description Abstract Corneal transparency is an essential characteristic necessary for normal vision. In response to microbial infection, the integrity of the cornea can become compromised as a result of the inflammatory response and the ensuing tissue pathology including neovascularization (NV) and collagen lamellae destruction. We have previously found complement activation contributes to cornea pathology-specifically, denervation in response to HSV-1 infection. Therefore, we investigated whether the complement system also played a role in HSV-1-mediated neovascularization. Using wild type (WT) and complement component 3 deficient (C3 KO) mice infected with HSV-1, we found corneal NV was accelerated associated with an increase in inflammatory monocytes (CD11b+CCR2+CD115+/−Ly6G−Ly6Chigh), macrophages (CD11b+CCR2+CD115+Ly6G−Ly6Chigh) and a subpopulation of granulocytes/neutrophils (CD11b+CCR2−CD115+Ly6G+Ly6Clow). There were also increases in select pro-inflammatory and pro-angiogenic factors including IL-1α, matrix metalloproteinases (MMP)-2, MMP-3, MMP-8, CXCL1, CCL2, and VEGF-A that coincided with increased inflammation, neovascularization, and corneal opacity in the C3 KO mice. The difference in inflammation between WT and C3 KO mice was not driven by changes in virus titer. However, viral antigen clearance was hindered in C3 KO mouse corneas suggesting the complement system has a dynamic regulatory role within the cornea once an inflammatory cascade is initiated by HSV-1.
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spelling doaj.art-181959dcb960480a9c1dd4c4285e64862022-12-21T19:32:06ZengNature PortfolioScientific Reports2045-23222021-05-0111111510.1038/s41598-021-89818-9An intact complement system dampens cornea inflammation during acute primary HSV-1 infectionAdrian Filiberti0Grzegorz B. Gmyrek1Amanda N. Berube2Derek J. Royer3Daniel J. J. Carr4Departments of Ophthalmology, The University of Oklahoma Health Sciences Center (OUHSC)Departments of Ophthalmology, The University of Oklahoma Health Sciences Center (OUHSC)Departments of Ophthalmology, The University of Oklahoma Health Sciences Center (OUHSC)Departments of Ophthalmology, The University of Oklahoma Health Sciences Center (OUHSC)Departments of Ophthalmology, The University of Oklahoma Health Sciences Center (OUHSC)Abstract Corneal transparency is an essential characteristic necessary for normal vision. In response to microbial infection, the integrity of the cornea can become compromised as a result of the inflammatory response and the ensuing tissue pathology including neovascularization (NV) and collagen lamellae destruction. We have previously found complement activation contributes to cornea pathology-specifically, denervation in response to HSV-1 infection. Therefore, we investigated whether the complement system also played a role in HSV-1-mediated neovascularization. Using wild type (WT) and complement component 3 deficient (C3 KO) mice infected with HSV-1, we found corneal NV was accelerated associated with an increase in inflammatory monocytes (CD11b+CCR2+CD115+/−Ly6G−Ly6Chigh), macrophages (CD11b+CCR2+CD115+Ly6G−Ly6Chigh) and a subpopulation of granulocytes/neutrophils (CD11b+CCR2−CD115+Ly6G+Ly6Clow). There were also increases in select pro-inflammatory and pro-angiogenic factors including IL-1α, matrix metalloproteinases (MMP)-2, MMP-3, MMP-8, CXCL1, CCL2, and VEGF-A that coincided with increased inflammation, neovascularization, and corneal opacity in the C3 KO mice. The difference in inflammation between WT and C3 KO mice was not driven by changes in virus titer. However, viral antigen clearance was hindered in C3 KO mouse corneas suggesting the complement system has a dynamic regulatory role within the cornea once an inflammatory cascade is initiated by HSV-1.https://doi.org/10.1038/s41598-021-89818-9
spellingShingle Adrian Filiberti
Grzegorz B. Gmyrek
Amanda N. Berube
Derek J. Royer
Daniel J. J. Carr
An intact complement system dampens cornea inflammation during acute primary HSV-1 infection
Scientific Reports
title An intact complement system dampens cornea inflammation during acute primary HSV-1 infection
title_full An intact complement system dampens cornea inflammation during acute primary HSV-1 infection
title_fullStr An intact complement system dampens cornea inflammation during acute primary HSV-1 infection
title_full_unstemmed An intact complement system dampens cornea inflammation during acute primary HSV-1 infection
title_short An intact complement system dampens cornea inflammation during acute primary HSV-1 infection
title_sort intact complement system dampens cornea inflammation during acute primary hsv 1 infection
url https://doi.org/10.1038/s41598-021-89818-9
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