Natural immune signaling pathways: New pathogen-related molecular patterns and corresponding patterns in bacteria identify receptors.

I. On August 16th, Nature published a research paper entitled Alpha-kinase 1 is a cytosolic innate immune en-fighter for ADP-heptose, the first time bacteria have been found and proven in the study of the new pathogen-related molecular patterns and corresponding pattern recognition receptors in the bacteria. The medium ADP-Hep enters the host cell and binds to the kinase ALPK1 N-end domain, and stimulates the activation and cytokine production of NF-sp. The system has shown that the metabolite ADP-Hep, which is present in all Gram-negative bacteria and some Gram-positive bacteria, is a true PAMP that can pass through the cell membranes of mammals. AlPK1 kinase recognition, which is widely expressed as PRR, induces the production of cytokines.
the study first identified strains that activate natural immunodeficiency using transposonscreening, and found that specific glycoean metabolites that act as pathogen-related molecular patterns were ADP-heptose (ADP-beta-D-manno-heptose) rather than HBP.
using CRISPR-Cas9 high-throughput screening, the team further identified genetically defective cells that could not identify ADP-heptose stimulation, and determined that the pattern recognition receptor for ADP-heptose was ALPK1.
finally, through various methods, such as biochemistry, structural biology and genetics, from molecular mechanisms, gene defect cells and mice and other levels, proved that the immune system through ALPK1 to identify Thegram negative bacteria ADP-heptose, so as to achieve pattern recognition and downstream immune signal transduction of the molecular mechanism.
this article also identified the new pathogen-related molecular patterns and corresponding pattern recognition receptors, and depicts a new natural immune signal transduction pathway, with extraordinary original and practical application value.
this article for the first time systematically demonstrated that the metaboliteSA ADP-Hep present in all Gram-negative bacteria and some Gram-positive bacteria, as PAMP, is able to induce the production of cytokines through the cell membrane of mammals, and is widely expressed as PRR, and induces the production of cytokines, so ADP-Hep has great potential for application as immunomodulators and vaccine adjures.
this study reveals a third pattern-identification pathway for lipid polysaccharide LPS, in addition to TLR4 (Poltorak et al., 1998) and caspase-11 (Shi et al., 2014), in which ALPK1 identifies not the LPS itself but the core metabolism of the LPS synthesis process.
these findings will guide us in exploring the nature of other PAMP-PRR effects and help us understand the invasion mechanisms of bacterial pathogenic bacteria, providing a target for drug development for related diseases.
References 1. Poltorak, A., He, X., Smirnova, I, Liu, M.Y., Van Huffel, C., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., et al. (1998). Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282, 2085-2088.2. Shi, J., Zhao, Y., Wang, Y., Gao, W., Ding, J., Li, P., Hu, L., and Shao, F. (2014). Acly caspases are innate immune eos for intracellular LPS. Nature 514, 187-192. If you are interested in knowledge about "natural immunity", the small editor has integrated its signaling pathways for your reference.
II, the natural immune signaling pathway overview of natural immunity, refers to the individual is born with, a wide range of action, not specific antigen simmunity, so also called nonspecific immunity.
the natural immune system can recognize both the structural components of pathogens, known as pathogen-related molecular patterns (Pathogen-associated moleculars, or PAMPs), or the body's own damage-related molecules, known as damage-related molecular patterns (Damage-associated molecular patterns, or DAMPs).
according to the classical pathogen natural immune process, the natural immune response has three periods.
begins with a rapid reaction period, in which some of the immune system's existing effect molecules act.
then enters an early induced response, in which various cells involved in the inflammatory response are activated and the removal of the pathogen is exercised.
finally, a specific immune response mediated by lymphocytes (this phase is adaptive).
the characteristics of these three periods are as follows: the inherent immune period (0-4h) when the pathogen enters the body, the main part of the immune system to identify and remove pathogens is some existing effect molecules (so very timely, rapid), such as antimicrobial peptides, lysozyme, acute protein, certain cytokines and so on.
, the complement bypass pathway is activated, and the chemators secreted by infected tissue cells attract the recruitment of phagocytosis (which can devour and kill pathogens).
if the pathogen is not removed through these effect steps, then move on to the next period: the inherent immune response period.
an inherent immune response period (4-96h) early induced response, phagocytosis cells identify pathogens and activate, swallowing function is enhanced, devouring kill pathogens;
if this still does not completely remove the pathogen, then enter the adaptive immune response period.
the late induced response of adaptive immune response period (96h after), the unremoved pathogen simply or antigen-raised cell ingestion into the peripheral lymphatic organs and tissues, by macrophages, dendritic lymphocyte processing after the antigen to MHC-peptide complex to The T-cell, induce the production of specific T-cell immune response, B-cell directly identify antigens after induced specific liquid immune response, and finally effective and effective and effective.
the classical signaling pathways involved in the identification and early response stages of pathogens or damaged molecules include: Toll-like receptor (TLR) signaling pathway (membrane surface and internal receptor) C-type coagulation receptor (CLR) signaling pathway (membrane surface receptor) inflammatory small body and cell focal death signaling pathway (intra-cell plasma receptor) RIG-I-MA signaling pathway (intracellular receptor) cGAS-STING signaling pathway (intra-cell receptor) It also includes a number of immune and inflammatory-related signaling pathways widely present in various immune cells: JAK-STAT signaling pathways (downstream signaling of multiple cytokines) NF-kB signaling pathways (downstream signaling transmission common to multiple immune cell response processes) T-cell receptor signaling pathways (T immune cell regulation-related signals) Transmission) B-cell receptor signaling pathways (B-immune cell regulation-related signaling) immunomonitoring point-related signaling pathways (immune co-activation and co-inhibition molecular regulatory pathways) These pathways work together at different stages when immune cell induction PAMPs or DAMPs, together forming a natural immune signaling pathway system.
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