Yu, T., Schuette, F., Christofi, M., Forrester, J. V., Graham, G. J. and Kuffova, L. (2022) The atypical chemokine receptor-2 fine-tunes the immune response in herpes stromal keratitis. Frontiers in Immunology, 13, 1054260. (doi: 10.3389/fimmu.2022.1054260) (PMID:36518752) (PMCID:PMC9742518)
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Abstract
Herpes stromal keratitis (HSK) is a blinding corneal disease caused by herpes simplex virus-1 (HSV-1), a common pathogen infecting most of the world’s population. Inflammation in HSK is chemokine-dependent, particularly CXCL10 and less so the CC chemokines. The atypical chemokine receptor-2 (ACKR2) is a decoy receptor predominantly for pro-inflammatory CC chemokines, which regulates the inflammatory response by scavenging inflammatory chemokines thereby modulating leukocyte infiltration. Deletion of ACKR2 exacerbates and delays the resolution of the inflammatory response in most models. ACKR2 also regulates lymphangiogenesis and mammary duct development through the recruitment of tissue-remodeling macrophages. Here, we demonstrate a dose-dependent upregulation of ACKR2 during corneal HSV-1 infection. At an HSV inoculum dose of 5.4 x 105 pfu, but not at higher dose, ACKR2 deficient mice showed prolonged clinical signs of HSK, increased infiltration of leukocytes and persistent corneal neovascularization. Viral clearance and T cell activation were similar in ACKR2-/- and wild type mice, despite a transient diminished expression of CD40 and CD86 in dendritic cells. The data suggest that ACKR2 fine-tunes the inflammatory response and the level of neovascularization in the HSK.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was funded by Fight for Sight, The Eye Charity (CSO project grant award: 3031-3032). The Development Trust of the University of Aberdeen (Saving Sight in Grampian) (Grant No. RG-12663 and RG-14251). The Wellcome Trust Investigator Award (Grant No. 217093/Z/19/Z) and an MRC Programme Grant (Grant No. MRV0109721). The National Natural Science Foundation for Young Scholars of China (Grant No. 81900833). |
| Keywords: | Atypical chemokine receptor-2, herpes stromal keratitis, antigen presenting cell, adaptive immunity, neovascularization. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Schuette, Dr Fabian and Graham, Professor Gerard |
| Authors: | Yu, T., Schuette, F., Christofi, M., Forrester, J. V., Graham, G. J., and Kuffova, L. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Research Centre: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology |
| Journal Name: | Frontiers in Immunology |
| Publisher: | Frontiers Media |
| ISSN: | 1664-3224 |
| ISSN (Online): | 1664-3224 |
| Copyright Holders: | Copyright © 2022 Yu, Schuette, Christofi, Forrester, Graham and Kuffova |
| First Published: | First published in Frontiers in Immunology 13: 1054260 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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