| الوصف: |
Type I interferons (IFNs) are very important innate cytokines that influence local and systemic immune responses. They can play beneficial roles through their antiviral properties and augmentation of host immune response; however, IFN responses can also have detrimental outcomes for the host. Our preliminary data suggests that during chikungunya virus (CHIKV) infection—a re-emerging alphavirus that causes outbreaks of febrile arthritis—IFNs exhibit both beneficial and detrimental functions. Additionally, these diverse properties of IFNs are likely the result of signaling on stromal and structural cells like fibroblasts and endothelial cells. The contribution of stromal cells to in vivo host immune responses remains poorly defined, even though these cell types are among the first cells to respond to vaccinations and vector-borne infectious diseases. Our proposed research will test the hypothesis that type I IFNs play distinct roles throughout the course of CHIKV infection due to the responses of distinct stromal cell populations. The studies proposed will utilize mouse genetics to conditionally delete IFN signaling from different stromal cells, temporal antibody blocking strategies, and RNA sequencing techniques to interrogate how IFNs impact these specific cells at different times during CHIKV infection. These findings have the potential to impact our understanding of the host response to vector-transmitted viruses and vaccines. |