The atypical chemokine receptor-2 fine-tunes the immune response in herpes stromal keratitis

Tian Yu, Fabian Schuette, Maria Christofi, John V. Forrester, Gerard J. Graham, Lucia Kuffova

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Article number1054260
JournalFrontiers in Immunology
Publication statusPublished - 28 Nov 2022


Dive into the research topics of 'The atypical chemokine receptor-2 fine-tunes the immune response in herpes stromal keratitis'. Together they form a unique fingerprint.

Cite this