| Autor: |
Ying Shiang Lim, Aisha G. Lee, Xiaoping Jiang, Jason M. Scott, Adjoa Cofie, Sandeep Kumar, Dania Kennedy, David J. Granville, Haina Shin |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 42, Iss 4, Pp 112410- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2023.112410 |
| Popis: |
Summary: 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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