• Molecules and Cells
• /
• v.44 no.6
• /
• pp.384-391
• /
• 2021

The recent appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people around the world and caused a global pandemic of coronavirus disease 2019 (COVID-19). It has been suggested that uncontrolled, exaggerated inflammation contributes to the adverse outcomes of COVID-19. In this review, we summarize our current understanding of the innate immune response elicited by SARS-CoV-2 infection and the hyperinflammation that contributes to disease severity and death. We also discuss the immunological determinants behind COVID-19 severity and propose a rationale for the underlying mechanisms.

• BMB Reports
• /
• v.53 no.9
• /
• pp.449-452
• /
• 2020

The inner ear is a complex and delicate structure composed of the cochlea and the vestibular system. To maintain normal auditory function, strict homeostasis of the inner ear is needed. A proper immune response against infection, thus, is crucial. Also, since excessive immune reaction can easily damage the normal architecture within the inner ear, the immune response should be fine regulated. The exact mechanism how the inner ear's immune response, specifically the innate immunity, is regulated was unknown. Recently, we reported a protein selectively localized in the inner ear during bacterial infection, named cochlin, as a possible mediator of such regulation. In this review, the immunological function of cochlin and the mechanism behind its role within inner ear immunity is summarized. Cochlin regulates innate immunity by physically entrapping pathogens within scala tympani and recruiting innate immune cells. Such mechanism enables efficient removal of pathogen while preserving the normal inner ear structure from inflammatory damage.

• Toxicological Research
• /
• v.25 no.4
• /
• pp.159-173
• /
• 2009

Nuclear factor erythroid derived 2-related factor-2 (Nrf2) is a master transcription regulator of antioxidant and cytoprotective proteins that mediate cellular defense against oxidative and inflammatory stresses. Disruption of cellular stress response by Nrf2 deficiency causes enhanced susceptibility to infection and related inflammatory diseases as a consequence of exacerbated immune-mediated hypersensitivity and autoimmunity. The cellular defense capacity potentiated by Nrf2 activation appears to balance the population of $CD4^+$ and $CD8^+$ of lymph node cells for proper innate immune responses. Nrf2 can negatively regulate the activation of pro-inflammatory signaling molecules such as p38 MAPK, NF-${\kappa}B$, and AP-1. Nrf2 subsequently functions to inhibit the production of pro-inflammatory mediators including cytokines, chemokines, cell adhesion molecules, matrix metalloproteinases, COX-2 and iNOS. Although not clearly elucidated, the antioxidative function of genes targeted by Nrf2 may cooperatively regulate the innate immune response and also repress the expression of pro-inflammatory mediators.

• International Journal of Industrial Entomology and Biomaterials
• /
• v.45 no.2
• /
• pp.43-48
• /
• 2022

Bombyx mori is a representative industrial insect and is used in silk production. Additionally, it serves as an insect model in molecular studies. To date, various molecular studies on its physiological characteristics, including the innate immune response and cuticular melanization, have been conducted. The melanization, including cuticular melanization, in insects is controlled by the prophenoloxidase-activating system, which is also involved in their innate immune response. In this review, to better understand the molecular mechanisms underlying the prophenoloxidase-activating system in the silkworm, the roles of five biomolecules, namely tyrosine hydroxylase, prophenoloxidase-activating enzyme, phenoloxidase, serine protease homolog, and immulectin, are discussed.

• BMB Reports
• /
• v.38 no.2
• /
• pp.128-150
• /
• 2005

Invertebrate animals, which lack adaptive immune systems, have developed other systems of biological host defense, so called innate immunity, that respond to common antigens on the cell surfaces of potential pathogens. During the past two decades, the molecular structures and functions of various defense components that participated in innate immune systems have been established in Arthropoda, such as, insects, the horseshoe crab, freshwater crayfish, and the protochordata ascidian. These defense molecules include phenoloxidases, clotting factors, complement factors, lectins, protease inhibitors, antimicrobial peptides, Toll receptors, and other humoral factors found mainly in hemolymph plasma and hemocytes. These components, which together compose the innate immune system, defend invertebrate from invading bacterial, fungal, and viral pathogens. This review describes the present status of our knowledge concerning such defensive molecules in invertebrates.

• IMMUNE NETWORK
• /
• v.10 no.6
• /
• pp.181-187
• /
• 2010

Excessive alcohol consumption is one of the critical causative factors leading to alcoholic liver disease (ALD). ALD is characterized by a wide spectrum of liver damage, ranging from simple uncomplicated liver steatosis (fatty liver) to steatohepatitis and liver fibrosis/cirrhosis. It has been believed that the obvious underlying cause for ALD is due to hepatocyte death induced by alcohol itself. However, recent sparkling studies have shown that diverse immune responses contribute to ALD because liver is enriched with numerous immune cells. Especially, a line of evidence has suggested that innate immune cells such as Kupffer cells and natural killer (NK)/NKT cells are significantly involved in the pathogenesis of ALD via production of pro-inflammatory cytokines and other mediators. Indeed, more interestingly, hepatic stellate cells (HSCs), known as a major cell inducing liver steatosis and fibrosis, can be killed by liver NK cells, which could be suppressed by chronic alcohol consumption. In this review, with the view of liver as predominant innate immune organ, we describe the pathogenesis of ALD in which what roles of innate immune cells are and how they are interacting with HSCs.

• Proceedings of the Korea Society of Poultry Science Conference
• /
• 2004.11a
• /
• pp.33-34
• /
• 2004

Effect of dietary 2.0 % brown seaweed(Undaria pinnatifida) with bean extract on anti-oxidant system and TNF-$\alpha$ levels were evaluated in blood of 2 week-old broiler chicks activated innate immune response. Dietary brown seaweed and activation of innate immune response decreased MnSOD activities. while activation of innate immune reponse only increased CuZnSOD activities in erythrocyte cytosol. Activation of innate immune response lowered plasma SOD activity in birds fed seaweed with bean extract, increased peroxide levels, and decreased peroxidase activity in plasma. Brown seaweed with bean extract reduced TNF-$\alpha$ levels and increased ovotransferrins concentrations in plasma. The result indicated that dietary 2.0 % brown seaweed with bean extract affect innate immune response changing anti-oxidant system and TNF-$\alpha$ levels in broiler chicks.

• Molecules and Cells
• /
• v.27 no.1
• /
• pp.5-14
• /
• 2009

The availability of effective vaccines has had the most profound positive effect on improving the quality of public health by preventing infectious diseases. Despite many successful vaccines, there are still old and new emerging pathogens against which there is no vaccine available. A better understanding of how vaccines work for providing protection will help to improve current vaccines as well as to develop effective vaccines against pathogens for which we do not have a proper means to control. Recent studies have focused on innate immunity as the first line of host defense and its role in inducing adaptive immunity; such studies have been an intense area of research, which will reveal the immunological mechanisms how vaccines work for protection. Toll-like receptors (TLRs), a family of receptors for pathogen-associated molecular patterns on cells of the innate immune system, play a critical role in detecting and responding to microbial infections. Importantly, the innate immune system modulates the quantity and quality of long-term T and B cell memory and protective immune responses to pathogens. Limited studies suggest that vaccines which mimic natural infection and/or the structure of pathogens seem to be effective in inducing long-term protective immunity. A better understanding of the similarities and differences of the molecular and cellular events in host responses to vaccination and pathogen infection would enable the rationale for design of novel preventive measures against many challenging pathogens.

• Molecules and Cells
• /
• v.27 no.2
• /
• pp.243-250
• /
• 2009

Recent studies suggest a novel role of $HIF-1{\alpha}$ under nonhypoxic conditions, including antibacterial and antiviral innate immune responses. However, the identity of the pathogen-associated molecular pattern which triggers $HIF-1{\alpha}$ activation during the antiviral response remains to be identified. Here, we demonstrate that cellular administration of double-stranded nucleic acids, the molecular mimics of viral genomes, results in the induction of $HIF-1{\alpha}$ protein level as well as the increase in $HIF-1{\alpha}$ target gene expression. Whole-genome DNA microarray analysis revealed that double-stranded nucleic acid treatment triggers induction of a number of hypoxia-inducible genes, and induction of these genes are compromised upon siRNA-mediated $HIF-1{\alpha}$ knock-down. Interestingly, $HIF-1{\alpha}$ knock-down also resulted in down-regulation of a number of genes involved in antiviral innate immune responses. Our study demonstrates that $HIF-1{\alpha}$ activation upon nucleic acid-triggered antiviral innate immune responses plays an important role in regulation of genes involved in not only hypoxic response, but also immune response.

• Bulletin of the Korean Chemical Society
• /
• v.32 no.11
• /
• pp.3893-3898
• /
• 2011

Cellular uptake of double-stranded DNA (dsDNA) triggers strong innate immune responses via activation of NF-${\kappa}B$ transcription factor. However, the detailed mechanism of dsDNA-mediated innate immune response remains yet to be elucidated. Here, we show that the expression of tazarotene-induced gene 3 (TIG3) is dramatically induced by dsDNA stimulation, and the siRNA-mediated down-regulation of TIG3 mRNA results in significant suppression of dsDNA-triggered cytokine expression. Because TIG3 has been previously shown to physically interact with transglutaminase (TG) 1 to activate TG activity, and TG2 has been shown to induce NF-${\kappa}B$ activity by inducing $I{\kappa}B{\alpha}$ polymerization, we tested whether TG also plays a role in dsDNA-mediated innate immune response. Pre-treatment of TG inhibitors dramatically reduces dsDNA-triggered cytokine induction. We also show that, in HeLa cells, TG2 is the major TG, and TIG3 physically interacts with TG2. Combined together, our results suggest a novel mechanism of dsDNA-triggered innate immune response which is critically dependent on TIG3 and TG2.