DEEP WORK

Toll-like receptors (TLRs) are of interest to immunologists because of their front-line role in the initiation of innate immunity against invading pathogens1 . The signalling pathways activated by different TLRs have therefore been the focus of much research. TLR signalling involves a family of five adaptor proteins, which couple to downstream protein kinases that ultimately lead to the activati..

INTRODUCTIONThe innate immune system is the first line of host defense that induces immediate, non-specific immune responses against pathogens (1). Inflammation is part of the innate immune system and is initiated when the innate immune system recognizes invading pathogens or molecules from tissue injury through pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and inflamm..

VIRUSESViruses enter the host cell to hijack the machinery necessary for viral replication. Viral PAMPs can trigger innate immune responses either on the host cell surface, within the endosome, or in the cytoplasm.  Emerging evidence also suggests that innate immune detection might occur in the nucleus. Inflammasome sensors are activated in response to both DNA and RNA viruses, ensuring efficien..

\ GENERAL OVERVIEW OF INFLAMMASOME SENSING AND SIGNALING  Several cytoplasmic innate immune sensors form inflammasome complexes in response to PAMPs and DAMPs, including AIM2, NAIP, NLRC4, NLRP1, NLRP3, Pyrin, and caspase-11 (Fig. 1); further, mouse NLRP6, NLRP9b, and NLRP12 and human NLRP2, NLRP7, and IFN-inducible protein 16 (IFI16) have also been proposed to activate caspase-1 (5), although t..

TLR Signaling PathwaysRecognition of PAMPs by TLRs leads to transcriptional upregulation of distinct genes, depending on the TLRs and cell types involved (Figure 1). The difference in the signaling cascades activated by the individual TLRs can be partly explained by the TIR domain-containing adaptor molecules recruited to TLRs (Akira et al., 2006). There are five TIR domain-containing adaptors i..

TLRs and Their LigandsThe TLR family is one of the best-characterized PRR families and is responsible for sensing invading pathogens outside of the cell and in intracellular endosomes and lysosomes (Akira et al., 2006). TLRs are characterized by N-terminal leucine-rich repeats (LRRs) and a transmembrane region followed by a cytoplasmic Toll/IL-1R homology (TIR) domain. Ten TLRs have been identif..

IntroductionInflammation is a protective response by the body to ensure removal of detrimental stimuli, as well as a healing process for repairing damaged tissue (Medzhitov, 2008). Inflammation is caused by various factors such as microbial infection, tissue injury, and cardiac infarction. Classically, inflammation is characterized by five symptoms: redness, swelling, heat, pain, and loss of tis..

INTRODUCTIONBacteria, fungi, viruses, and protozoa are capable of causing infection, potentially leading to death of the host. The host immune system acts as a guardian and defends the body from challenge by pathogens. Both innate and adaptive immune systems contribute to the killing and clearance of invading microbes. Pattern recognition receptors (PRRs) of the innate immune system initiate sen..

Transepithelial transport mechanismsTransfer of substances across the intestinal epithelium can occur through either the transcellular route or the paracellular route. Paracellular transport is thought to be due to diffusion and solvent drag. The solvent drag hypothesis has been proposed by Pappenheimer (1993), and predicts that sugars and amino acids may, in part, be transported paracellularly...

IntroductionThe intestinal epithelium is a single cell layer protecting the organism against harmful agents in the lumen, and at the same time it is a site for nutrient, water and ion uptake. Integrity of the barrier and uptake mechanisms is crucial for the health and growth of the animal. However, many internal and external factors can influence the epithelium in both harmful and beneficial way..