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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Microbes and Innate Immunity
Volume 14 - 2024 | doi: 10.3389/fcimb.2024.1416105

Overexpression of NLRP12 enhances macrophage immune response and alleviates herpes simplex keratitis

Provisionally accepted
Jiaxuan Jiang Jiaxuan Jiang 1Di Zhang Di Zhang 1Wei Liu Wei Liu 2Jingya Yang Jingya Yang 1Fan Yang Fan Yang 1Junpeng Liu Junpeng Liu 1Kai Hu Kai Hu 1*
  • 1 Department of Ophthalmology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
  • 2 Linyi Bright Eye Hospital, Linyi, China

The final, formatted version of the article will be published soon.

    Herpes simplex keratitis (HSK) is a blinding disease caused by corneal infection of Herpes simplex virus type 1 (HSV-1). Effective clearance of HSV-1 from the infected cornea is critical for HSK management. Macrophages play an important part in the innate immune defense against viral infections. This study investigated the immunomodulatory role of NLRP12 in macrophage immune response during HSV-1 infection. We observed a significant decrease in NLRP12 expression post-infection in various macrophage cell lines. Overexpression of NLRP12 in macrophages reduced HSV-1 replication. Mechanistically, overexpression of NLRP12 triggered early and robust pyroptosis in response to HSV-1 infection, improving IL-18 production and activated downstream antiviral responses through the JAK-STAT signaling pathway. In vivo studies showed that ocular adoptive transfer of NLRP12-overexpression bone marrow derived macrophages (BMDMs) to mouse corneas alleviated HSK damages and reduced HSV-1 viral loads. NLRP12-overexpressing BMDMs improved the antiviral responses in the cornea and promoted the maturation of corneal-infiltrating macrophages and dendritic cells. NLRP12-overexpressing BMDMs also amplified the adaptive immune response in the submandibular draining lymph nodes. These findings highlight the role of NLRP12 in 2 macrophage-mediated immune response against HSV-1 infection and suggest its potential for possible immunotherapy for HSK.

    Keywords: Herpes simplex keratitis, Herpes simplex virus 1, NLRP12, macrophage, antiviral, pyroptosis

    Received: 11 Apr 2024; Accepted: 27 Jun 2024.

    Copyright: © 2024 Jiang, Zhang, Liu, Yang, Yang, Liu and Hu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Kai Hu, Department of Ophthalmology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.