Innate immunity and adjuvants Akira, Shizuo
Philosophical transactions of the Royal Society of London. Series B. Biological sciences,
10/2011, Volume:
366, Issue:
1579
Journal Article
Peer reviewed
Open access
Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. ...However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection.
The mammalian innate immune system detects the presence of microbial infection through germ line-encoded pattern recognition receptors (PRRs). Toll-like receptors, retinoic acid-inducible gene-I-like ...receptors and nucleotide-binding oligomerization domain-like receptors serve as PRRs that recognize different but overlapping microbial components. They are expressed in different cellular compartments such as the cell surface, endosome, lysosome or cytoplasm and activate specific signaling pathways that lead to expression of genes that tailor immune responses to particular microbes. This review summarizes recent insights into pathogen sensing by these PRRs and their signaling pathways.
The discovery of Toll-like receptors (TLRs) as components that recognize conserved structures in pathogens has greatly advanced understanding of how the body senses pathogen invasion, triggers innate ...immune responses and primes antigen-specific adaptive immunity. Although TLRs are critical for host defense, it has become apparent that loss of negative regulation of TLR signaling, as well as recognition of self molecules by TLRs, are strongly associated with the pathogenesis of inflammatory and autoimmune diseases. Furthermore, it is now clear that the interaction between TLRs and recently identified cytosolic innate immune sensors is crucial for mounting effective immune responses. Here we describe the recent advances that have been made by research into the role of TLR biology in host defense and disease.
Infection of cells by microorganisms activates the inflammatory response. The initial sensing of infection is mediated by innate pattern recognition receptors (PRRs), which include Toll-like ...receptors, RIG-I-like receptors, NOD-like receptors, and C-type lectin receptors. The intracellular signaling cascades triggered by these PRRs lead to transcriptional expression of inflammatory mediators that coordinate the elimination of pathogens and infected cells. However, aberrant activation of this system leads to immunodeficiency, septic shock, or induction of autoimmunity. In this Review, we discuss the role of PRRs, their signaling pathways, and how they control inflammatory responses.
Autophagy is a fundamental eukaryotic pathway that has multiple effects on immunity. Autophagy is induced by pattern recognition receptors and, through autophagic adaptors, it provides a mechanism ...for the elimination of intracellular microorganisms. Autophagy controls inflammation through regulatory interactions with innate immune signalling pathways, by removing endogenous inflammasome agonists and through effects on the secretion of immune mediators. Moreover, autophagy contributes to antigen presentation and to T cell homeostasis, and it affects T cell repertoires and polarization. Thus, as we discuss in this Review, autophagy has multitiered immunological functions that influence infection, inflammation and immunity.
Posttranscriptional control of mRNA regulates various biological processes, including inflammatory and immune responses. RNA-binding proteins (RBPs) bind
cis-
regulatory elements in the 3′ ...untranslated regions (UTRs) of mRNA and regulate mRNA turnover and translation. In particular, eight RBPs (TTP, AUF1, KSRP, TIA-1 TIAR, Roquin, Regnase, HuR, and Arid5a) have been extensively studied and are key posttranscriptional regulators of inflammation and immune responses. These RBPs sometimes collaboratively or competitively bind the same target mRNA to enhance or dampen regulatory activities. These RBPs can also bind their own 3′ UTRs to negatively or positively regulate their expression. Both upstream signaling pathways and microRNA regulation shape the interactions between RBPs and target RNA. Dysregulation of RBPs results in chronic inflammation and autoimmunity. Here, we summarize the functional roles of these eight RBPs in immunity and their associated diseases.
Innate immunity to virus infection Takeuchi, Osamu; Akira, Shizuo
Immunological reviews,
January 2009, Volume:
227, Issue:
1
Journal Article
Peer reviewed
Open access
The innate immune system is essential for the initial detection of invading viruses and subsequent activation of adaptive immunity. Three classes of receptors, designated retinoic acid-inducible gene ...I (RIG-I)-like receptors (RLRs), Toll-like receptors (TLRs), and nucleotide oligomerization domain (NOD)-like receptors (NLRs), sense viral components, such as double-stranded RNA (dsRNA), single-stranded RNA, and DNA. RLRs and TLRs play essential roles in the production of type I interferons (IFNs) and proinflammatory cytokines in cell type-specific manners. While the RLRs play essential roles in the recognition of RNA viruses in various cells, plasmacytoid dendritic cells utilize TLRs for detecting virus invasion. NLRs play a role in the production of mature interleukin-1β to dsRNA stimulation. Activation of innate immune cells is critical for mounting adaptive immune responses. In this review, we discuss recent advances in our understanding of the mechanisms of viral RNA recognition by these different types of receptors and its relation to acquired immune responses.
Toll‐like receptors (TLRs) and RIG‐I‐like receptors (RLRs) constitute distinct families of pattern‐recognition receptors that sense nucleic acids derived from viruses and trigger antiviral innate ...immune responses. TLR3, TLR7, and TLR9 are membrane proteins localized to the endosome that recognize viral double‐stranded RNA, single‐stranded RNA, and DNA, respectively, while RLRs, including RIG‐I, Mda5, and LGP2, are cytoplasmic proteins that recognize viral RNA. Upon recognition of these nucleic acid species, TLRs and RLRs recruit specific intracellular adaptor proteins to initiate signaling pathways culminating in activation of NF‐κB, MAP kinases, and IRFs that control the transcription of genes encoding type I interferon and other inflammatory cytokines, which are important for eliminating viruses. Here, we review recent insights into the signaling pathways initiated by TLR and RLR and their roles in innate and adaptive immune responses.
Mammalian immune response can be divided into innate and acquired immunity. Furthermore, much evidence has demonstrated that activation of innate immunity is a prerequisite to induction of acquired ...immunity. This paradigm shift has changed our thinking on the pathogenesis and treatment of infections, immune diseases, allergy, and cancers. (Communicated by Tadamitsu KISHIMOTO, M.J.A.)
Induction of the antiviral innate immune response depends on recognition of viral components by host pattern-recognition receptors. Members of the Toll-like receptor family have emerged as key ...sensors that recognize viral components such as nucleic acids. Toll-like receptor signaling results in the production of type I interferon and inflammatory cytokines and leads to dendritic cell maturation and establishment of antiviral immunity. Cells also express cytoplasmic RNA helicases that function as alternative pattern-recognition receptors through recognition of double-stranded RNA produced during virus replication. These two classes of pattern-recognition receptor molecules are expressed in different intracellular compartments and induce type I interferon responses via distinct signaling pathways.
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