Abstract
Innate and adaptive immunity work concertedly in vertebrates to restore homoeostasis following pathogen invasion or other insults. Like all homoeostatic circuits, immunity relies on an integrated system of sensors, transducers and effectors that can be analysed in cellular or molecular terms. At the cellular level, T and B lymphocytes act as an effector arm of immunity that is mobilised in response to signals transduced by innate immune cells that detect a given insult. These innate cells are spread around the body and include dendritic cells (DCs), the chief immune sensors of pathogen invasion and tumour growth. At the molecular level, DCs possess receptors that directly sense pathogen presence and tissue damage and that signal via transduction pathways to control antigen presentation or regulate a plethora of genes encoding effector proteins that regulate immunity. Notably, molecular circuits for pathogen detection are not confined to DCs or even to immune cells. All cells express sensors and transducers that monitor invasion by viruses and bacteria and elicit suitable effector barriers to pathogen propagation. Here, I discuss work from my laboratory that has contributed to our understanding of these issues over the years.
Highlights
The ability of all nucleated vertebrate cells to respond to virus invasion has been recognised since the discovery of interferons, virus-induced cytokines produced by both immune and non-immune cells
Following activation by viral RNA, RIG-I and MDA5 engage the mitochondrial adaptor protein MAVS initiating a signal transduction pathway that culminates in activation of transcription factors of the IRF and NF-jB families to induce type I and type III IFN gene expression (Fig 1)
Argonaute proteins that can “slice” viral RNAs bearing complementary sequences. This sequence-specific antiviral RNA interference (RNAi) response was thought to have been lost during vertebrate evolution of the IFN response even though the RNAi machinery itself has been preserved and is used for miRNAs generation and action
Summary
Innate and adaptive immunity work concertedly in vertebrates to restore homoeostasis following pathogen invasion or other insults. T and B lymphocytes act as an effector arm of immunity that is mobilised in response to signals transduced by innate immune cells that detect a given insult. These innate cells are spread around the body and include dendritic cells (DCs), the chief immune sensors of pathogen invasion and tumour growth. ISGs encode effectors of antiviral immunity elicited by a simple cell-intrinsic sensing and transducing immune circuit, albeit one involving IFN-mediated amplification and spread (Fig 1). RNAi is an antiviral strategy that is preserved from plants to humans and may be important in cellular niches in which the IFN response is attenuated
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