Abstract:
:The phagocyte NADPH oxidase, crucial for innate immunity, is dormant in resting cells, but becomes activated during phagocytosis to produce superoxide, a precursor of microbicidal oxidants. In activation of the oxidase, the multidomain protein p67(phox)plays a central role: it translocates to the membrane as a ternary complex with p47(phox)and p40(phox), and interacts with the small GTPase Rac to assemble with the membrane-integrated catalytic protein gp91(phox), leading to superoxide production. Here we show, using small-angle X-ray scattering (SAXS) analysis, that p67(phox)adopts an elongated conformation when it exists not only as a monomer but also as the heterotrimer. Although p67(phox)harbors an N-terminal TPR domain for binding to Rac and a p40(phox)-interacting PB1 domain, followed by an SH3 domain that associates with p47(phox), the present model suggests that no or few apparent associations occur between the domains. The positions of the protein-interaction domains in p67(phox)contribute to activation of the phagocyte NADPH oxidase: the first SH3 domain that is located between the TPR and PB1 domains positively regulates oxidase activation only when it is present at the correct position; the PB1 domain placed at this SH3 domain position inhibits the oxidase by interacting with p40(phox).
journal_name
J Innate Immunjournal_title
Journal of innate immunityauthors
Yuzawa S,Miyano K,Honbou K,Inagaki F,Sumimoto Hdoi
10.1159/000235656subject
Has Abstractpub_date
2009-01-01 00:00:00pages
543-55issue
6eissn
1662-811Xissn
1662-8128pii
000235656journal_volume
1pub_type
杂志文章abstract::Withdrawal of iron from serum (hypoferraemia) is a conserved innate immune antimicrobial strategy that can withhold this critical nutrient from invading pathogens, impairing their growth. Hepcidin (Hamp1) is the master regulator of iron and its expression is induced by inflammation. Mice lacking Hamp1 from birth rapid...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000447713
更新日期:2016-01-01 00:00:00
abstract::We demonstrated recently that Francisella tularensis profoundly impairs human neutrophil apoptosis, but how this is achieved is largely unknown. Herein we used human oligonucleotide microarrays to test the hypothesis that changes in neutrophil gene expression contribute to this phenotype, and now demonstrate that F. t...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000342430
更新日期:2013-01-01 00:00:00
abstract::Toll-like receptor (TLR) signaling is important in the initiation of immune responses and subsequent instigation of adaptive immunity. TLR2 recognizes bacterial lipoproteins and plays a central role in the host defense against bacterial infections, including those caused by Staphylococcus aureus. Many studies have dem...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000479100
更新日期:2017-01-01 00:00:00
abstract::Human immunodeficiency virus-1 (HIV-1) infection and the acquired immune deficiency syndrome (AIDS) pandemic remain global threats in the absence of a protective or a therapeutic vaccine. HIV-1 replication is reportedly inhibited by some cellular factors, including APOBEC3G (A3G) and APOBEC3F (A3F), which are well kno...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000339402
更新日期:2012-01-01 00:00:00
abstract::Calcium-independent phospholipase A2 (iPLA2) has been suggested to play an important role in the activation of caspase-1 induced by lipopolysaccharides (LPS). Here, we used pharmacological and genetic approaches to study the role of iPLA 2 in the activation of caspase-1. Bromoenol lactone (BEL), an inhibitor that was ...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000227263
更新日期:2009-01-01 00:00:00
abstract::Melanoma differentiation-associated gene 5 (MDA5) is a pattern recognition receptor that recognizes cytoplasmic viral double-stranded RNA (dsRNA) and initiates rapid innate antiviral responses. MDA5 forms a filament-like multimer along the dsRNA leading to oligomerization, which in turn activates the adaptor protein m...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000480740
更新日期:2018-01-01 00:00:00
abstract::Historically, the prevailing view in the field of invertebrate immunity was that invertebrates that do not possess acquired adaptive immunity rely on innate mechanisms with low specificity and no memory. Several recent studies have shaken this paradigm and suggested that the immune defenses of invertebrates are more c...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000345909
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Chronic inflammation and oxidative stress are hallmarks of chagasic cardiomyopathy (CCM). In this study, we determined if microparticles (MPs) generated during Trypanosoma cruzi (Tc) infection carry the host's signature of the inflammatory/oxidative state and provide information regarding the progression of ...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000451055
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:We have previously identified the upregulation of the innate immune response, neutrophil activation, and apoptosis during anaphylaxis using a microarray approach. This study aimed to validate the differential gene expression and investigate protein concentrations of "hub genes" and upstream regulators during...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000492301
更新日期:2019-01-01 00:00:00
abstract::γδ T cells function at the interface between innate and adaptive immunity and have well-demonstrated roles in response to infection, autoimmunity and tumors. A common characteristic of these seemingly disparate conditions may be cellular stress or death. However, the conditions under which ligands for γδ T cells are i...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000446498
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Alpha-synuclein (αS) is a nerve cell protein associated with Parkinson disease (PD). Accumulation of αS within the enteric nervous system (ENS) and its traffic from the gut to the brain are implicated in the pathogenesis and progression of PD. αS has no known function in humans and the reason for its accumul...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000477990
更新日期:2017-01-01 00:00:00
abstract::Mannose-binding lectin (MBL) is an innate immune system pattern recognition protein that kills a wide range of pathogenic microbes through complement activation. A substantial proportion of all human populations studied to date have MBL deficiency due to MBL2 polymorphisms, which potentially increases susceptibility t...
journal_title:Journal of innate immunity
pub_type: 杂志文章,评审
doi:10.1159/000228159
更新日期:2010-01-01 00:00:00
abstract::Different liver cell types are endowed with immunological properties, including cell-intrinsic innate immune functions that are important to initially control pathogen infections. However, a full landscape of expression and functionality of the innate immune signaling pathways in the major human liver cells is still m...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000489966
更新日期:2018-01-01 00:00:00
abstract::Toll-like receptors (TLRs) are key molecules in innate immunity that recognize a variety of pathogen-associated molecular patterns. Activation of TLRs by their agonists initiates several signaling cascades, which eventually result in the expression of immune modifiers. Despite the fact that MCPIP1 is reported as an im...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000339826
更新日期:2013-01-01 00:00:00
abstract::Ficolins are a group of oligomeric lectins with subunits consisting of both collagen-like and fibrinogen-like domains. The majority of ficolins identified in vertebrates and invertebrates to date recognize N-acetylglucosamine (GlcNAc). X-ray crystallographic analysis of human ficolins has shown that the fibrinogen-lik...
journal_title:Journal of innate immunity
pub_type: 杂志文章,评审
doi:10.1159/000228160
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Oncolytic vesicular stomatitis virus (VSV) can be delivered intravenously to target primary and metastatic lesions, but the interaction between human peripheral blood leukocytes (PBLs) and VSV remains poorly understood. Our study aimed to assess the overall immunological consequences of ex vivo infection of ...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000485143
更新日期:2018-01-01 00:00:00
abstract::Monocytes (Mos) play an important role in the pathogenesis of intestinal mucosal inflammation. This study aims to investigate the mechanism by which the intestinal epithelial cell-derived thrombospondin 1 (TSP1) modulates Mo properties and regulates intestinal inflammatory responses. In this study, the production of T...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000398799
更新日期:2015-01-01 00:00:00
abstract::There is increasing evidence that the immune system is regulated by circadian rhythms. A wide range of immune parameters, such as the number of red blood cells and peripheral blood mononuclear cells as well as the level of critical immune mediators, such as cytokines, undergo daily fluctuations. Current experimental d...
journal_title:Journal of innate immunity
pub_type: 杂志文章,评审
doi:10.1159/000342427
更新日期:2013-01-01 00:00:00
abstract::Neutrophil-derived antimicrobial peptides and proteins (AMPs) play an important role in the defense against microbes. Absence of defense is illustrated by neutropenic patients with frequent bacterial and fungal infections. However, the specificity of the antimicrobial effects has not been adequately described. We set ...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000317665
更新日期:2010-01-01 00:00:00
abstract::Immunoglobulin A nephropathy (IgAN) is the most common form of glomerulonephritis throughout the world. A majority (approx. 60%) of patients with IgAN experience disease exacerbations associated with an acute respiratory or gastrointestinal illness that appears to represent a viral infection. However, the exact mechan...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000345255
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Pseudomonas aeruginosa (PS) infection results in severe morbidity and mortality, especially in immune-deficient populations. Aerobic exercise (AE) modulates the immune system, but its effects on the outcomes of pulmonary PS infection in elderly mice are unknown. METHODS:BALB/c mice (24 weeks old) were rando...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000488953
更新日期:2018-01-01 00:00:00
abstract::Streptococcus pyogenes is an important human pathogen that causes a variety of diseases including life-threatening invasive diseases, such as toxic shock and deep tissue infections. Although S. pyogenes are classically considered extracellular pathogens, a clinical significance of an intracellular source has been emph...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000317635
更新日期:2010-01-01 00:00:00
abstract::Psoriasis is one of the most common immune-mediated disorders. There is evidence that it is mediated by Th1 and, more recently, Th17 cells. The cytokine pattern, particularly the dominance of TNF-α, implicates the innate immune system in psoriasis pathogenesis. Of the many components of the innate immune system known ...
journal_title:Journal of innate immunity
pub_type: 杂志文章,评审
doi:10.1159/000328011
更新日期:2011-01-01 00:00:00
abstract::Activation of complement leads to generation of the 3 anaphylatoxins C3a, C4a, and C5a. Although all 3 peptides are structurally similar, only C3a and C5a share a similar functional profile that includes the classic inflammatory activities and, more recently, developmental homing and regenerative properties among othe...
journal_title:Journal of innate immunity
pub_type: 杂志文章,评审
doi:10.1159/000371423
更新日期:2015-01-01 00:00:00
abstract::Listeria monocytogenes is a facultative intracellular pathogen which can infect Drosophila melanogaster. Upon infection, Drosophila mounts an immune response including antimicrobial peptide production and autophagy activation. A set of previously published results prompted us to study the role of the deubiquitinating ...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000360293
更新日期:2014-01-01 00:00:00
abstract::In in vitro experiments, Chlamydia pneumoniae has been shown to infect macrophages and to accelerate foam cell formation. It has been hypothesized that the C. pneumoniae infection affects foam cell formation by suppressing the expression of liver X receptors (LXR), but whether such an event occurs in human atheroscler...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000327522
更新日期:2011-01-01 00:00:00
abstract::Neutrophils are the most abundant cell type involved in the innate immune response. They are rapidly recruited to sites of injury or infection where they engulf and kill invading microorganisms. Neutrophil apoptosis, the process of programmed cell death that prevents the release of neutrophil histotoxic contents, is t...
journal_title:Journal of innate immunity
pub_type: 杂志文章,评审
doi:10.1159/000284367
更新日期:2010-01-01 00:00:00
abstract::NK cells play a central role in innate immunity, acting directly through cell-mediated cytotoxicity and by secreting cytokines. TNFα activation of TNFR2 enhances NK cell cytotoxicity, but its effects on the other essential function of NK cells - cytokine production, for which IFNγ is paramount - are poorly defined. We...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000448077
更新日期:2016-01-01 00:00:00
abstract::Urinary tract infection (UTI) is a prominent global health care burden. Although UTI is readily treated with antibiotics in healthy adults, complicated cases in immune-compromised individuals and the emerging antibiotic resistance of several uropathogens have accelerated the need for new treatment strategies. Here, we...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000499342
更新日期:2019-01-01 00:00:00
abstract::Fibroblasts are known to eliminate intracellular bacteria, but the lethal hit of the bactericidal mechanism has not been defined. We show that primary embryonic and established fibroblasts can be induced by interferons or by intracellular bacterial infection to express a perforin-like mRNA previously described as macr...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000345249
更新日期:2013-01-01 00:00:00