Antigens, Bacterial ; immunology ; Drug Resistance, Bacterial ; immunology ; Signal Transduction ; immunology ; Vaccines, Subunit ; immunology

Microbial components and the endogenous molecules released from damaged cells can stimulate germ-line-encoded pattern recognition receptors (PRRs) to transduce signals to the hub of the innate immune signaling network-the adaptor proteins MyD88/TRIF/MAVS/STING/Caspase-1, where integrated signals relay to the relevant transcription factors IRF3/IRF7/NF-κB/ AP-1 and the signal transducer and activator of transcription 6 (STAT6) to trigger the expression of type I interferons and inflammatory cytokines or the assembly of inflammasomes. Most pleiotropic cytokines are secreted and bind to specific receptors, activating the signaling pathways including JAK-STAT for the proliferation, differentiation and functional capacity of immune cells. This review focuses on several critical adaptors in innate immune signaling cascades and recent progress in their molecular mechanisms.
Adaptive Immunity ; Adaptor Proteins, Signal Transducing ; immunology ; metabolism ; Animals ; Humans ; Immunity, Innate ; Signal Transduction ; immunology

The cyclic GMP-AMP (cGAMP) synthase (cGAS) has been identified as a cytosolic double stranded DNA sensor that plays a pivotal role in the type I interferon and inflammation responses via the STING-dependent signaling pathway. In the past several years, a growing body of evidence has revealed that cGAS is also localized in the nucleus where it is associated with distinct nuclear substructures such as nucleosomes, DNA replication forks, the double-stranded breaks, and centromeres, suggesting that cGAS may have other functions in addition to its role in DNA sensing. However, while the innate immune function of cGAS is well established, the non-canonical nuclear function of cGAS remains poorly understood. Here, we review our current understanding of the complex nature of nuclear cGAS and point to open questions on the novel roles and the mechanisms of action of this protein as a key regulator of cell nuclear function, beyond its well-established role in dsDNA sensing and innate immune response.
Cell Nucleus/immunology* ; Humans ; Immunity, Innate ; Nucleotidyltransferases/immunology* ; Signal Transduction/immunology*

The Notch signaling pathway is conserved from Drosophila to mammals and is critically involved in developmental processes. In the immune system, it has been established that Notch signaling regulates multiple steps of T and B cell development in both central and peripheral lymphoid organs. Relative to the well documented role of Notch signaling in lymphocyte development, less is known about its role in regulating myeloid lineage development and function, especially in the context of acute and chronic inflammation. In this review article, we will describe the evidence accumulated during the recent years to support a key regulatory role of the Notch pathway in innate immune and inflammatory responses and discuss the potential implications of such regulation for pathogenesis and therapy of inflammatory disorders.
Animals ; B-Lymphocytes ; immunology ; pathology ; Humans ; Inflammation ; immunology ; pathology ; Receptors, Notch ; immunology ; Signal Transduction ; immunology ; T-Lymphocytes ; immunology ; pathology

In this research, we studied the formation of Drosophila melanogaster FADD (Fas-associated death domain-containing protein) amyloid fiber and its influence on signal transduction in IMD (Immune deficiency) signaling pathway to better understand the regulation mechanism of Drosophila innate immune signaling pathway, which will provide reference for the immune regulation in other species. First, we purified dFADD protein expressed in Escherichia coli and performed Sulfur flavin T binding and transmission electron microscopy to identify the dFADD amyloid fibers formed in vitro. Then we investigated the formation of dFADD polymers in S2 cells using SDD-AGE and confocal microscope. We also constructed dFADD mutants to find out which domain is essential to fiber formation and its effect on IMD signal transduction. Our results revealed that dFADD could be polymerized to form amyloid fiber polymers in vitro and inside the cells. Formation of fibers relies on DED (Death-effector domain) domain of dFADD, since DED domain-deleted mutant existed as a monomer. Dual luciferase reporter assay showed that intact DED domain was required for the induction of downstream antimicrobial peptides, indicating that fiber formation was the key to IMD signal transduction. Our study revealed the role of dFADD in mediating the cascade between IMD and Dredd in the IMD signaling pathway by forming amyloid fibers, suggesting an evolutionarily conserved regulatory mechanism of innate immune signaling pathway.
Animals ; Drosophila Proteins ; biosynthesis ; immunology ; Drosophila melanogaster ; immunology ; Fas-Associated Death Domain Protein ; biosynthesis ; immunology ; Immunity, Innate ; immunology ; Signal Transduction

Interferons (IFNs) are cytokines playing an important role in immune responses. Interferons are classified into two distinct types according to specific interferon receptors(IFNR). Type I IFNs include IFN-α and IFN-β, whereas IFN-γ is type II IFN. It is well known that type I IFNs have important roles in the host defense against viruses through activation of interferon receptor A (IFNAR). However, many recent studies have also demonstrated that type I IFNs have effects on immune responses to bacterial infection. This review focuses on the immune regulation of type I IFN-mediated signal pathways in bacterial infections such as Listeria monocytogenes, Streptococcus, Mycobacterium tuberculosis, Bacillus anthracis, Legionella, Pseudomonas aeruginosa and others.
Animals ; Bacterial Infections ; immunology ; Humans ; Immunity, Innate ; Interferon Type I ; immunology ; Signal Transduction

Toll like receptor (TLR) can specifically recgnize pathogen-associated molecular patterns (PAMPs) and is considered as an important link between innate and adaptive immunity. It has been shown that TLR plays an important role in the pathogenesis and pathophysiology of a variety of skin diseases. Moreover, TLR agonists have exhibited promising therapeutic effects on the disease models and are expected to be novel vaccine adjuvants. Investigations of the underlying mechanism will give new insights into these diseases. This review will discuss the relationship between TLR and pathogenesis and management of some cutaneous diseases.
Adaptive Immunity ; Immunity, Innate ; Signal Transduction ; Skin Diseases ; immunology ; metabolism ; Toll-Like Receptors ; immunology ; metabolism ; physiology

OBJECTIVETo investigate the effect of RNA interfering TLR4 signal pathway on phagocytosis of Kupffer cells.

METHODSRAW2647 mice mononuclear macrophage leukemia cells were observed. The tested group was interfered by Tlr4-mus-1567 RNA which had the best result confirmed by QPCR, cells interfered by Negative Control RNA as NC group, and normal cell as control. We perform the phagocytosis test on each group.

RESULTSThe tested group has lower phagocytes percentage than control (17.67% +/- 3.51% vs 32.00% +/- 3.00%, P < 0.01), and lower phagocytic index (46.33% +/- 7.51% vs 82.00% +/- 6.08%, P < 0.01).

CONCLUSIONSDecreased phagocytic activity was observed on Kupffer cells by RNA interference.

Animals ; Kupffer Cells ; immunology ; Mice ; Phagocytosis ; RNA Interference ; Signal Transduction ; Toll-Like Receptor 4 ; genetics ; immunology

Polysaccharides extracted from various sources are natural active substances, which may lead to the activation of macrophage via multiple pathways and mechanisms. This article intends to illustrate the signaling pathways of polysaccharides from plants, fungi, algae and other sources, to identify the mechanisms on the molecular level, and to explore the novel target immunomodulatory agents.
Animals ; Humans ; Macrophage Activation ; drug effects ; immunology ; Macrophages ; drug effects ; immunology ; metabolism ; Polysaccharides ; pharmacology ; Signal Transduction

Liver Diseases ; immunology ; metabolism ; Signal Transduction ; Toll-Like Receptors ; immunology ; metabolism