Cooperative anti-influenza activities of respiratory innate immune proteins and neuraminidase inhibitor

2005 ◽  
Vol 288 (5) ◽  
pp. L831-L840 ◽  
Author(s):  
Mitchell R. White ◽  
Erika Crouch ◽  
Martin van Eijk ◽  
Max Hartshorn ◽  
Lily Pemberton ◽  
...  
Keyword(s):  
Influenza A ◽  
Scavenger Receptor ◽  
Lavage Fluid ◽  
Neuraminidase Inhibitor ◽  
Innate Immune ◽  
Dependent Manner ◽  
Viral Neutralization ◽  
Cooperative Effects ◽  
Calcium Dependent ◽  
Viral Hemagglutinin

The surfactant collectins, surfactant proteins A and D (SP-A and D), and scavenger receptor-rich glycoprotein 340 (gp340) inhibit influenza A virus (IAV) in the following order of potency: SP-D>gp340>SP-A. SP-D binds in a calcium-dependent manner to carbohydrate attachments on the viral hemagglutinin (HA) and neuraminidase (NA). By contrast, gp340 and SP-A act like mucins in that they provide sialic acid ligands that bind to the viral HA. In this study, SP-D, SP-A, and gp340 showed cooperative antiviral interactions. These cooperative effects were most evident in viral aggregation but were also observed in at least some hemagglutination inhibition and viral neutralization assays. The mechanism of binding between gp340 and SP-D was further characterized using monoclonal antibodies. Although gp340 can bind to SP-D at a site distinct from the mannan-binding site, binding of gp340 to SP-D did not contribute to cooperative antiviral interactions. SP-D and mucin showed cooperative interactions, apparently dependent on NA inhibition by SP-D. The commercial NA inhibitor oseltamivir had a similar effect and also enhanced the neutralizing activity of SP-A and bronchoalveolar lavage fluid. Hence, oseltamivir collaborates with innate immune proteins in inhibiting the initial infection of epithelial cells.

scholarly journals LOX-1 scavenger receptor mediates calcium-dependent recognition of phosphatidylserine and apoptotic cells

2005 ◽  
Vol 393 (1) ◽  
pp. 107-115 ◽  
Author(s):  
Jane E. Murphy ◽  
Daryl Tacon ◽  
Philip R. Tedbury ◽  
Jonathan M. Hadden ◽  
Stuart Knowling ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Low Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Dependent Manner ◽  
Oxidized Low Density Lipoprotein ◽  
Bivalent Cation ◽  
Calcium Dependent

The LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1) scavenger receptor regulates vascular responses to oxidized-low-density-lipoprotein particles implicated in atherosclerotic plaque formation. LOX-1 is closely related to C-type lectins, but the mechanism of ligand recognition is not known. Here we show that human LOX-1 recognizes a key cellular phospholipid, PS (phosphatidylserine), in a Ca2+-dependent manner, both in vitro and in cultured cells. A recombinant, folded and glycosylated LOX-1 molecule binds PS, but not other phospholipids. LOX-1 recognition of PS was maximal in the presence of millimolar Ca2+ levels. Mg2+ was unable to substitute for Ca2+ in LOX-1 binding to PS, indicating a Ca2+-specific requirement for bivalent cations. LOX-1-mediated recognition of PS-containing apoptotic bodies was dependent on Ca2+ and was decreased to background levels by bivalent-cation chelation, LOX-1-blocking antibodies or PS-containing liposomes. The LOX-1 membrane protein is thus a Ca2+-dependent phospholipid receptor, revealing novel recognition of phospholipids by mammalian lectins.

Scavenger receptor class A type I/II (CD204) null mice fail to develop fibrosis following silica exposure

2005 ◽  
Vol 289 (2) ◽  
pp. L186-L195 ◽  
Author(s):  
Celine A. Beamer ◽  
Andrij Holian
Keyword(s):  
Scavenger Receptor ◽  
Lavage Fluid ◽  
Type I ◽  
Dependent Manner ◽  
Wild Type ◽  
Focal Lesions ◽  
Silica Exposure ◽  
Class A

Alveolar macrophages express the class A scavenger receptor (CD204) (Babaev VR, Gleaves LA, Carter KJ, Suzuki H, Kodama T, Fazio S, and Linton MF. Arterioscler Thromb Vasc Biol 20: 2593–2599, 2000); yet its role in vivo in lung defense against environmental particles has not been clearly defined. In the current study, CD204 null mice (129Sv background) were used to investigate the link between CD204 and downstream events of inflammation and fibrosis following silica exposure in vivo. CD204−/− macrophages were shown to recognize and uptake silica in vitro, although this response was attenuated compared with 129Sv wild-type mice. The production of tumor necrosis factor-α in lavage fluid was significantly enhanced in CD204 null mice compared with wild-type mice following silica exposure. Moreover, after exposure to environmental particles, CD204−/− macrophages exhibited improved cell viability in a dose-dependent manner compared with wild-type macrophages. Finally, histopathology from a murine model of chronic silicosis in 129Sv wild-type mice displayed typical focal lesions, interstitial thickening with increased connective tissue matrix, and cellular infiltrate into air space. In contrast, CD204−/− mice exhibited little to no deposition of collagen, yet they demonstrated enhanced accumulation of inflammatory cells largely composed of neutrophils. Our findings point to an important role of CD204 in mounting an efficient and appropriately regulated immune response against inhaled particles. Furthermore, these results indicate that the functions of CD204 are critical to the development of fibrosis and the resolution of inflammation.

Hepcidin regulation by innate immune and infectious stimuli

Blood ◽  
2011 ◽  
Vol 118 (15) ◽  
pp. 4129-4139 ◽  
Author(s):  
Andrew E. Armitage ◽  
Lucy A. Eddowes ◽  
Uzi Gileadi ◽  
Suzanne Cole ◽  
Natasha Spottiswoode ◽  
...  
Keyword(s):  
Influenza A ◽  
Acute Infection ◽  
Transferrin Saturation ◽  
Hepatoma Cells ◽  
Innate Immune ◽  
Dependent Manner ◽  
Human Hepatoma Cells ◽  
Hepcidin Expression

Abstract Hepcidin controls the levels and distribution of iron, an element whose availability can influence the outcome of infections. We investigated hepcidin regulation by infection-associated cytokines, pathogen-derived molecules, and whole pathogens in vitro and in vivo. We found that IL-22, an effector cytokine implicated in responses to extracellular infections, caused IL-6–independent hepcidin up-regulation in human hepatoma cells, suggesting it might represent an additional inflammatory hepcidin agonist. Like IL-6, IL-22 caused phosphorylation of STAT3 and synergized with BMP6 potentiating hepcidin induction. In human leukocytes, IL-6 caused potent, transient hepcidin up-regulation that was augmented by TGF-β1. Pathogen-derived TLR agonists also stimulated hepcidin, most notably the TLR5 agonist flagellin in an IL-6–dependent manner. In contrast, leukocyte hepcidin induction by heat-killed Candida albicans hyphae was IL-6–independent, but partially TGF-β–dependent. In a murine acute systemic candidiasis model, C albicans strongly stimulated hepcidin, accompanied by a major reduction in transferrin saturation. Similarly, hepcidin was up-regulated with concomitant lowering of serum iron during acute murine Influenza A/PR/8/34 virus (H1N1) infection. This intracellular pathogen also stimulated hepcidin expression in leukocytes and hepatoma cells. Together, these results indicate that hepcidin induction represents a component of the innate immune response to acute infection, with the potential to affect disease pathogenesis.

scholarly journals Salivary agglutinin and lung scavenger receptor cysteine-rich glycoprotein 340 have broad anti-influenza activities and interactions with surfactant protein D that vary according to donor source and sialylation

2005 ◽  
Vol 393 (2) ◽  
pp. 545-553 ◽  
Author(s):  
Kevan L. Hartshorn ◽  
Antoon Ligtenberg ◽  
Mitchell R. White ◽  
Martin van Eijk ◽  
Max Hartshorn ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Influenza A ◽  
Scavenger Receptor ◽  
Surfactant Protein ◽  
Sialic Acids ◽  
Surfactant Protein D ◽  
Influenza A Viruses ◽  
Viral Neutralization ◽  
Antiviral Activities ◽  
Innate Defence

We previously found that scavenger receptor cysteine-rich gp-340 (glycoprotein-340), isolated from lung or saliva, directly inhibits human IAVs (influenza A viruses). We now show that salivary gp-340 has broad antiviral activity against human, equine and porcine IAV strains. Although lung and salivary gp-340 are identical in protein sequence, salivary gp-340 from one donor had significantly greater antiviral activity against avian-like IAV strains which preferentially bind sialic acids in α(2,3) linkage. A greater density of α(2,3)-linked sialic acids was present on the salivary gp-340 from this donor as compared with salivary gp-340 from another donor or several preparations of lung gp-340. Hence, the specificity of sialic acid linkages on gp-340 is an important determinant of anti-IAV activity. Gp-340 binds to SP-D (surfactant protein D), and we previously showed that lung gp-340 has co-operative interactions with SP-D in viral neutralization and aggregation assays. We now report that salivary gp-340 can, in some cases, strongly antagonize certain antiviral activities of SP-D. This effect was associated with greater binding of salivary gp-340 to the carbohydrate recognition domain of SP-D as compared with the binding of lung gp-340. These findings may relate to inter-individual variations in innate defence against highly pathogenic IAV and to effects of aspiration of oral contents on SP-D-mediated lung functions.

scholarly journals RIG-I Signaling via MAVS Is Dispensable for Survival in Lethal Influenza Infection In Vivo

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Wenxin Wu ◽  
Xiaoqiu Wang ◽  
Wei Zhang ◽  
Lili Tian ◽  
J. Leland Booth ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza A ◽  
Influenza Infection ◽  
Lavage Fluid ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Downstream Signaling ◽  
Cytokine Responses

Retinoic acid-inducible gene I (RIG-I) is an important regulator of virus-induced antiviral interferons (IFNs) and proinflammatory cytokines. It requires interaction with an adaptor molecule, mitochondrial antiviral-signaling protein (MAVS), to activate downstream signaling pathways. To elucidate the mechanism(s) by which RIG-I-dependent recognition of IAV infection in vivo triggers innate immune responses, we infected mutant mice lacking RIG-I or MAVS with influenza A virus (IAV) and measured their innate immune responses. As has previously been demonstrated with isolated deletion of the virus recognition receptors TLR3, TLR7, and NOD2, RIG-I or MAVS knockout (KO) did not result in higher mortality and did not reduce IAV-induced cytokine responses in mice. Infected RIG-I KO animals displayed similar lung inflammation profiles as did WT mice, in terms of the protein concentration, total cell count, and inflammatory cell composition in the bronchoalveolar lavage fluid. RNA-Seq results demonstrated that all types of mice exhibited equivalent antiviral and inflammatory gene responses following IAV infection. Together, the results indicated that although RIG-I is important in innate cytokine responses in vitro, individual deletion of the genes encoding RIG-I or MAVS did not change survival or innate responses in vivo after IAV infection in mice.

scholarly journals Ca2+-Dependent Protein Kinase 6 Enhances KAT2 Shaker Channel Activity in Arabidopsis thaliana

2021 ◽  
Vol 22 (4) ◽  
pp. 1596
Author(s):  
Elsa Ronzier ◽  
Claire Corratgé-Faillie ◽  
Frédéric Sanchez ◽  
Christian Brière ◽  
Tou Cheu Xiong
Keyword(s):  
Arabidopsis Thaliana ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Physical Interaction ◽  
Fluorescence Lifetime Imaging ◽  
Dependent Manner ◽  
In Planta ◽  
Knock Out ◽  
Calcium Dependent ◽  
Dependent Protein

Post-translational regulations of Shaker-like voltage-gated K+ channels were reported to be essential for rapid responses to environmental stresses in plants. In particular, it has been shown that calcium-dependent protein kinases (CPKs) regulate Shaker channels in plants. Here, the focus was on KAT2, a Shaker channel cloned in the model plant Arabidopsis thaliana, where is it expressed namely in the vascular tissues of leaves. After co-expression of KAT2 with AtCPK6 in Xenopuslaevis oocytes, voltage-clamp recordings demonstrated that AtCPK6 stimulates the activity of KAT2 in a calcium-dependent manner. A physical interaction between these two proteins has also been shown by Förster resonance energy transfer by fluorescence lifetime imaging (FRET-FLIM). Peptide array assays support that AtCPK6 phosphorylates KAT2 at several positions, also in a calcium-dependent manner. Finally, K+ fluorescence imaging in planta suggests that K+ distribution is impaired in kat2 knock-out mutant leaves. We propose that the AtCPK6/KAT2 couple plays a role in the homeostasis of K+ distribution in leaves.

scholarly journals EXPRESS: Retrospective study of clinical characteristics and viral etiologies of patients with viral pneumonia in Beijing

2021 ◽  
pp. 204589402110110
Author(s):  
Xiang Zhao ◽  
Yao Meng ◽  
Duo Li ◽  
Zhaomin Feng ◽  
Weijuan Huang ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Influenza A ◽  
Clinical Characteristics ◽  
Ebola Virus ◽  
Treatment Strategies ◽  
Lavage Fluid ◽  
Viral Pneumonia ◽  
Chip Technology ◽  
Viral Influenza ◽  
Simplex Virus

Aims: The virus is common in patients with viral pneumonia. However, the viral etiology and clinical features of patients with viral pneumonia in China remain unclear. The main purpose of this study was to analyze the viral causes and epidemiology of patients with viral pneumonia in Beijing, which can significantly improve the pertinence and accuracy of clinical treatment of the disease. Methods: Firstly, 1,539 respiratory specimens of pneumonia (oropharyngeal swabs, nasopharyngeal swabs, saliva samples and bronchoalveolar lavage fluid) were collected from 19 hospitals in Beijing from September 2015 to August 2018. Then, TaqMan low-density microfluidic chip technology was used to detect viral pneumonia specimens in 1,539 respiratory tract specimens of pneumonia, and determine the types of viral bacteria in them. Lastly, the analysis of demographic, clinical and etiological data of patients with viral pneumonia was performed. Results: The results showed that among the 1,539 respiratory tract specimens with pneumonia, 760 were detected as viral pneumonia specimens, with a positive rate of 49.4%. Among which, 467 were infected with mono-viral and 293 were infected with multi-viral. Influenza A virus (Flu A), mycoplasma pneumoniae (MPn), ebola virus (EBV) and herpes simplex virus type 1 (HSV-1) were the major viral components in the samples of these patients. Furthermore, these viral species were significantly associated with sample sources, onset season and certain clinical characteristics. Discussion: Our findings may provide corresponding treatment strategies for viral pneumonia patients infected with specific viruses.

scholarly journals The Antiinfective Effects of Velvet Antler of Formosan Sambar Deer (Cervus unicolor swinhoei) onStaphylococcus aureus-Infected Mice

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Ting-Yeu Dai ◽  
Chih-Hua Wang ◽  
Kun-Nan Chen ◽  
I-Nung Huang ◽  
Wei-Sheng Hong ◽  
...  
Keyword(s):  
Lipoteichoic Acid ◽  
Lavage Fluid ◽  
Dependent Manner ◽  
Protective Mechanisms ◽  
Velvet Antler ◽  
Sambar Deer ◽  
Dose Dependent ◽  
Cervus Unicolor

We assayed the effects of velvet antler (VA) of Formosan sambar deer (Cervus unicolor swinhoei) and its extracts on the anti-infective activity against pathogenicStaphylococcus aureus in vitroandin vivoin this study.In vitrodata indicated that the VA extracts stimulated the proliferation of resting splenocytes and macrophages in a dose-dependent manner up to the highest concentration used (150 μg mL−1). The production of proinflammatory cytokines (TNF-α, IL-6, IL-12) by lipoteichoic acid was significantly suppressed after being cocultured with the VA extracts in a dose-dependent manner. Animal test inS. aureus-infected mice demonstrated that the numbers of bacteria determined in the kidneys and peritoneal lavage fluid ofS. aureus-infected mice were significantly higher than those found in the same organs of mice pretreated with the VA samples. Moreover, the highly enhanced phagocytic activity of macrophages was further verified afterin vitrotreatment with the VA samples. The protective mechanisms of the VA samples might include an immune enhancer and an inflammatory cytokine suppressor.

scholarly journals Masking of β(1-3)-Glucan in the Cell Wall of Candida albicans from Detection by Innate Immune Cells Depends on Phosphatidylserine

2014 ◽  
Vol 82 (10) ◽  
pp. 4405-4413 ◽  
Author(s):  
Sarah E. Davis ◽  
Alex Hopke ◽  
Steven C. Minkin ◽  
Anthony E. Montedonico ◽  
Robert T. Wheeler ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
De Novo ◽  
Invasive Disease ◽  
Innate Immune ◽  
Dependent Manner ◽  
Content Type ◽  
Immune Effector ◽  
Host Interactions ◽  
Innate Immune Effector

ABSTRACTThe virulence ofCandida albicansin a mouse model of invasive candidiasis is dependent on the phospholipids phosphatidylserine (PS) and phosphatidylethanolamine (PE). Disruption of the PS synthase geneCHO1(i.e.,cho1Δ/Δ) eliminates PS and blocks thede novopathway for PE biosynthesis. In addition, thecho1Δ/Δ mutant's ability to cause invasive disease is severely compromised. Thecho1Δ/Δ mutant also exhibits cell wall defects, and in this study, it was determined that loss of PS results in decreased masking of cell wall β(1-3)-glucan from the immune system. In wild-typeC. albicans, the outer mannan layer of the wall masks the inner layer of β(1-3)-glucan from exposure and detection by innate immune effector molecules like the C-type signaling lectin Dectin-1, which is found on macrophages, neutrophils, and dendritic cells. Thecho1Δ/Δ mutant exhibits increases in exposure of β(1-3)-glucan, which leads to greater binding by Dectin-1 in both yeast and hyphal forms. The unmasking of β(1-3)-glucan also results in increased elicitation of TNF-α from macrophages in a Dectin-1-dependent manner. The role of phospholipids in fungal pathogenesis is an emerging field, and this is the first study showing that loss of PS inC. albicansresults in decreased masking of β(1-3)-glucan, which may contribute to our understanding of fungus-host interactions.

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