دورية أكاديمية
Overexpression of NLRP12 enhances antiviral immunity and alleviates herpes simplex keratitis via pyroptosis/IL-18/IFN-γ signaling.
| العنوان: | Overexpression of NLRP12 enhances antiviral immunity and alleviates herpes simplex keratitis via pyroptosis/IL-18/IFN-γ signaling. |
|---|---|
| المؤلفون: | Jiang J; Department of Ophthalmology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, China., Shen W; Department of Ophthalmology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, China., He Y; Department of Ophthalmology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, China., Liu J; Department of Ophthalmology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, 321 Zhongshan Road, Nanjing 210008, China., Ouyang J; Department of Ophthalmology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, China., Zhang C; Department of Ophthalmology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, China., Hu K; Department of Ophthalmology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, China. Electronic address: kai_hu@nju.edu.cn. |
| المصدر: | International immunopharmacology [Int Immunopharmacol] 2024 Aug 20; Vol. 137, pp. 112428. Date of Electronic Publication: 2024 Jun 21. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam ; New York : Elsevier Science, c2001- |
| مواضيع طبية MeSH: | Pyroptosis* , Keratitis, Herpetic*/immunology , Keratitis, Herpetic*/virology , Interleukin-18*/metabolism , Interleukin-18*/immunology , Interferon-gamma*/metabolism , Interferon-gamma*/immunology , Herpesvirus 1, Human*/immunology , Herpesvirus 1, Human*/physiology , Signal Transduction* , Mice, Inbred C57BL*, Animals ; Humans ; Mice ; Cornea/virology ; Cornea/immunology ; Cornea/pathology ; Female ; Virus Replication ; Intracellular Signaling Peptides and Proteins/metabolism ; Intracellular Signaling Peptides and Proteins/genetics ; Disease Models, Animal ; Inflammasomes/metabolism ; Inflammasomes/immunology ; Immunity, Innate |
| مستخلص: | Herpes simplex keratitis (HSK) is a blinding disease caused by herpes simplex virus type 1 (HSV-1) infection, and rapid eradication of the virus from the affected cornea is imperative. Nod-like receptors (NLRs) are intracellular innate immune sensors closely associated with cell death, inflammation and immune responses. In this study, we investigated the role of NLRP12 in the antiviral immunology in HSK and the underlying mechanisms. We found that NLRP12 expression was significantly decreased in HSV-1-infected human corneal epithelial cells (HCE-Ts) and HSK mouse corneas. Overexpression of NLRP12 significantly reduced viral replication in infected HCE-Ts and functioned through inflammasome-mediated pyroptosis and downstream IL-18-IFN-γ axis. In HSK mouse models, overexpression of NLRP12 reduced viral replication in the cornea and alleviated HSK symptoms. This resulted from enhanced antiviral immune responses including the activation of specific immune cells in both the cornea and the draining lymph nodes. Specifically, the NLRP12-IL-18-IFN-γ axis regulated the interaction between infected corneal epithelial cells and macrophages. In conclusion, our study identified a role of NLRP12 in mediating pyroptosis and regulating antiviral immune responses. This novel finding opens the possibilities of NLRP12 as a viable target in the therapeutic strategies for HSV-1 infection. (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Antiviral immunity; Herpes simplex keratitis; Inflammasome; NLRP12; Pyroptosis |
| المشرفين على المادة: | 0 (Interleukin-18) 82115-62-6 (Interferon-gamma) 0 (NLRP12 protein, mouse) 0 (Intracellular Signaling Peptides and Proteins) 0 (Inflammasomes) |
| تواريخ الأحداث: | Date Created: 20240622 Date Completed: 20240710 Latest Revision: 20240805 |
| رمز التحديث: | 20240805 |
| DOI: | 10.1016/j.intimp.2024.112428 |
| PMID: | 38908077 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1878-1705 |
|---|---|
| DOI: | 10.1016/j.intimp.2024.112428 |