Abstract
MHC class I molecules are key in the presentation of antigen and initiation of adaptive CD8+ T cell responses. In addition to its classical activity, MHC I may possess nonclassical functions. We have previously identified a regulatory role of MHC I in TLR signaling and antibacterial immunity. However, its role in innate antiviral immunity remains unknown. In this study, we found a reduced viral load in MHC I-deficient macrophages that was independent of type I IFN production. Mechanically, MHC I mediated viral suppression by inhibiting the type I IFN signaling pathway, which depends on SHP2. Cross-linking MHC I at the membrane increased SHP2 activation and further suppressed STAT1 phosphorylation. Therefore, our data revealed an inhibitory role of MHC I in type I IFN response to viral infection and expanded our understanding of MHC I and antigen presentation.
Highlights
The innate immune system is the first line defense for viral infection
To examine whether Major histocompatibility complex (MHC) I is involved in innate antiviral immune responses, we first infected macrophages from MHC I-deficient mice and littermate control mice with VSV
Both the percentage and the mean fluorescence intensity (MFI) of GFP-positive cells were decreased in MHC I-/- macrophages (Figure 1(e))
Summary
After recognition of certain pathogen-associated molecular patterns (PAMPs), diverse pattern recognition receptors (PRRs) trigger antiviral immune responses by inducing type I interferon (IFN) [1]. Type I IFN exerts its antiviral function by binding to its receptors and activating JAK-STAT signaling, which induces the expression of IFNstimulated genes (ISGs) [3]. Both the production and downstream signaling of type I IFN are necessary for host innate antiviral immunity. Targeting type I IFN is the major mechanism employed by viruses to evade the host immune defense, and viruses have developed diverse strategies to circumvent the type I IFN system [4]. Many regulators have been identified [5, 6], the details of fine-tuned IFN production and function remain unknown
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