Abstract
Influenza viruses cause annual epidemics and occasional pandemics that have claimed the lives of millions. Both innate and acquired immunity are essential for protection against influenza virus. A viral infection is initially sensed by the host innate system, triggering a rapid antiviral response that involves the release of proinflammatory cytokines, and eventually leads to the activation of the adaptive immune response. The innate immune response is initiated when cellular pathogen recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPs). The innate immune response by antigen presenting cells (APCs), including dendritic cells (DCs) and macrophages, is initiated quickly to protect from overwhelming infectious organisms, but with time, also can activate the adaptive immune response to the invading pathogens. The adaptive immune response is essential for purging a diverse repertoire of invading pathogens, and CD4+ and CD8+ T cells are required for successful eradication of pathogens. Initial studies have indicated that the interaction of Notch and Notch ligands plays a critical role during development, and further, the Notch system is an important bridge between APCs and T-cell communication circuits. However, the role of Notch system during influenza virus infection is still unknown. Here we review our recent study which shows that Notch signaling through macrophage-dependent Delta-like 1 (Dll1) is critical in providing an anti-viral response during influenza virus infection by linking innate and acquired immunity.
