Interferon-λ inhibits immunopathology and boosts T cell–mediated immunity in a mouse model of mucosal viral infection
Emily Feng, Alexa Mansour, Elizabeth Balint, Alyssa Mark, Sofia Tramonte, Jonathan K. Monteiro, Madison Read, Marie Joe Adaimy, Zhou Xing, Matthias Mack, Sergei V. Kotenko, Deanna M. Santer, Ali A. Ashkar
Emily Feng, Alexa Mansour, Elizabeth Balint, Alyssa Mark, Sofia Tramonte, Jonathan K. Monteiro, Madison Read, Marie Joe Adaimy, Zhou Xing, Matthias Mack, Sergei V. Kotenko, Deanna M. Santer, Ali A. Ashkar
View: Text | PDF
Research Article Immunology Infectious disease Inflammation

Interferon-λ inhibits immunopathology and boosts T cell–mediated immunity in a mouse model of mucosal viral infection

Abstract

Interferon lambda (IFN-λ) has emerged as a critical inducer of immune regulation in addition to its mucosal antiviral properties. However, the cellular and molecular mechanisms that govern its dual role during viral infections remain unclear. Here, we discovered that mucosal delivery of IFN-λ abrogates the herpes simplex virus type 2–induced (HSV-2-induced) vaginal tissue pathology observed in the absence of type I IFN signaling, through drastically inhibiting IL-6 production. At the same time, we demonstrated that IFN-λ rescued local production of CD4+ T cell–dependent IFN-γ, which is essential for protection against the development of toxic megacolon following genital HSV-2 infection. Mechanistically, we found that IFN-λ enhances the differentiation of CCR2+Ly6Chi cells into monocyte-derived antigen-presenting cells, thereby boosting T cell responses. In vivo depletion of CCR2+ cells abrogated this phenomenon. Together, these findings suggest that IFN-λ orchestrates a potent antiviral response, inhibiting hyperinflammatory responses while selectively augmenting effector T cell function. This study positions IFN-λ as a promising therapeutic candidate for enhancing local antiviral immunity and offers new insights into the regulation of immune responses in the context of mucosal viral infections.

Authors

Emily Feng, Alexa Mansour, Elizabeth Balint, Alyssa Mark, Sofia Tramonte, Jonathan K. Monteiro, Madison Read, Marie Joe Adaimy, Zhou Xing, Matthias Mack, Sergei V. Kotenko, Deanna M. Santer, Ali A. Ashkar

×
Problems with a PDF?

This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.

Having trouble reading a PDF?

PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.

Having trouble saving a PDF?

Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.

Having trouble printing a PDF?

  1. Try printing one page at a time or to a newer printer.
  2. Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
  3. Make sure you are using the latest version of Adobe's Acrobat Reader.

Supplemental data - Download (1.52 MB)

Advertisement