| First Author | Jeon S | Year | 2018 |
| Journal | J Immunol | Volume | 200 |
| Issue | 11 | Pages | 3711-3719 |
| PubMed ID | 29669784 | Mgi Jnum | J:263220 |
| Mgi Id | MGI:6159555 | Doi | 10.4049/jimmunol.1700417 |
| Citation | Jeon S, et al. (2018) PD-L1/B7-H1 Inhibits Viral Clearance by Macrophages in HSV-1-Infected Corneas. J Immunol 200(11):3711-3719 |
| abstractText | Immune privilege helps protect the cornea from damaging inflammation but can also impair pathogen clearance from this mucosal surface. Programmed death-ligand 1 (PD-L1 or B7-H1) contributes to corneal immune privilege by inhibiting the function of a variety of immune cells. We asked whether programmed death-1 (PD-1)/PD-L1 interaction regulates HSV-1 clearance from infected corneas. We show that PD-L1 is constitutively expressed in the corneal epithelium and is upregulated upon HSV-1 corneal infection, with peak expression on CD45(+) cells NK cells, dendritic cells, neutrophils, and macrophages and CD45(-) corneal epithelial cells at 4 d postinfection (dpi). As early as 1 dpi, HSV-1-infected corneas of B7-H1(-/-) mice as compared with wild-type mice showed increased chemokine expression and this correlated with increased migration of inflammatory cells into the viral lesions and decreased HSV-1 corneal titers. Local PD-L1 blockade caused a similar increase in viral clearance, suggesting a local effect of PD-1/PD-L1 in the cornea. The enhanced HSV-1 clearance at 2 dpi resulting from PD-1/PD-L1 blockade is mediated primarily by a monocyte/macrophage population. Studies in bone marrow chimeras demonstrated enhanced viral clearance when PD-L1 was absent only from nonhematopoietic cells. We conclude that PD-L1 expression on corneal cells negatively impacts the ability of the innate immune system to clear HSV-1 from infected corneas. |
