| First Author | Lim YS | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 4 | Pages | 112410 |
| PubMed ID | 37071533 | Mgi Jnum | J:335544 |
| Mgi Id | MGI:7470604 | Doi | 10.1016/j.celrep.2023.112410 |
| Citation | Lim YS, et al. (2023) NK cell-derived extracellular granzyme B drives epithelial ulceration during HSV-2 genital infection. Cell Rep 42(4):112410 |
| abstractText | Genital herpes is characterized by recurrent episodes of epithelial blistering. The mechanisms causing this pathology are ill defined. Using a mouse model of vaginal herpes simplex virus 2 (HSV-2) infection, we show that interleukin-18 (IL-18) acts upon natural killer (NK) cells to promote accumulation of the serine protease granzyme B in the vagina, coinciding with vaginal epithelial ulceration. Genetic loss of granzyme B or therapeutic inhibition by a specific protease inhibitor reduces disease and restores epithelial integrity without altering viral control. Distinct effects of granzyme B and perforin deficiency on pathology indicates that granzyme B acts independent of its classic cytotoxic role. IL-18 and granzyme B are markedly elevated in human herpetic ulcers compared with non-herpetic ulcers, suggesting engagement of these pathways in HSV-infected patients. Our study reveals a role for granzyme B in destructing mucosal epithelium during HSV-2 infection, identifying a therapeutic target to augment treatment of genital herpes. |
