Immunology

Since their discovery, innate lymphoid cells (ILCs) have been the subject of intense research. As their name implies, ILCs are innate cells of lymphoid origin, and can be grouped into subsets based on their cytotoxic activity, cytokine profile, and the transcriptional requirements during ILC differentiation. The main ILC groups are “killer” ILCs, comprising NK cells, and “helper-like” ILCs (including ILC1s, ILC2s, and ILC3s). This review examines the origin, differentiation stages, and plasticity of murine and human ILC3s. ILC3s express the retinoic acid receptor (RAR) related orphan receptor RORγt and the signature cytokines IL-22 and IL-17. Fetal ILC3s or lymphoid tissue inducer cells are required for lymphoid organogenesis, while postnatally developing ILC3s are important for the generation of intestinal cryptopatches and isolated lymphoid follicles as well as for the defence against pathogens and epithelial homeostasis. Here, we discuss the transcription factors and exogenous signals (including cytokines, nutrients and cell-to-cell interaction) that drive ILC3 lineage commitment and acquisition of their distinctive effector program.

Chen explains that each of the three type I interferon-triggering pathways recognizes a particular signal of infection. Invading viruses and bacteria often deliver and replicate their genetic material in the main compartment of the cell known as the cytoplasm, where host DNA is not normally found. A sensor protein called RIG-I detects viral RNA in this cytosolic compartment, which usually indicates the presence of an RNA virus. Cytosolic DNA, which can be introduced by a variety of microbes, including bacteria, DNA viruses, and retroviruses, is detected by a sensor called cGAS, which Chen's lab discovered in 2012. Nucleic acids in membrane-bound compartments called endosomes also indicate viral infection, and are detected by sensors called Toll-like receptors.

Each of these three receptors cooperates with its own adaptor protein to relay its message that an invader is present and interferon is needed. Toll-like receptors work with an adaptor called TRIF, the cGAS receptor works with the adaptor protein STING, and the RIG-I receptor pairs with an adaptor that Chen's lab discovered in 2005 called MAVS.

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Abstract

Toll-like receptors (TLRs) are the best studied family of pattern-recognition receptors (PRRs) whose task is to rapidly recognize evolutionarily conserved structures on the invading microorganisms. Through binding to these patterns, TLRs trigger a number of proinflammatory and antimicrobial responses, playing a key role in the first line of defense against the pathogens promoting also adaptive immunity responses. Growing amounts of data suggest that single nucleotide polymorphisms (SNPs) on the various human TLR proteins are associated with altered susceptibility to infection. This review summarizes the role of TLRs in innate immunity, their ligands and signaling and focuses to the TLR SNPs which have been linked to infectious disease susceptibility.

other posts about TLRs

http://www.scoop.it/t/immunology?q=TLR