scholarly journals C-type lectins and extracellular vesicles in virus-induced NETosis

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Pei-Shan Sung ◽  
Shie-Liang Hsieh
Keyword(s):  
Extracellular Vesicles ◽  
Viral Infections ◽  
Multiple Organ ◽  
Intercellular Adhesion Molecule ◽  
Inflammatory Reactions ◽  
Intravascular Coagulopathy ◽  
Encephalomyelitis Virus ◽  
Toll Like Receptor 2 ◽  
Lectin Family ◽  
Virus Spreading

AbstractDysregulated formation of neutrophil extracellular traps (NETs) is observed in acute viral infections. Moreover, NETs contribute to the pathogenesis of acute viral infections, including those caused by the dengue virus (DV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Furthermore, excessive NET formation (NETosis) is associated with disease severity in patients suffering from SARS-CoV-2-induced multiple organ injuries. Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and other members of C-type lectin family (L-SIGN, LSECtin, CLEC10A) have been reported to interact with viral glycans to facilitate virus spreading and exacerbates inflammatory reactions. Moreover, spleen tyrosine kinase (Syk)-coupled C-type lectin member 5A (CLEC5A) has been shown as the pattern recognition receptor for members of flaviviruses, and is responsible for DV-induced cytokine storm and Japanese encephalomyelitis virus (JEV)-induced neuronal inflammation. Moreover, DV activates platelets via CLEC2 to release extracellular vesicles (EVs), including microvesicles (MVs) and exosomes (EXOs). The DV-activated EXOs (DV-EXOs) and MVs (DV-MVs) stimulate CLEC5A and Toll-like receptor 2 (TLR2), respectively, to enhance NET formation and inflammatory reactions. Thus, EVs from virus-activated platelets (PLT-EVs) are potent endogenous danger signals, and blockade of C-type lectins is a promising strategy to attenuate virus-induced NETosis and intravascular coagulopathy.

scholarly journals Role of Innate Inflammation in the Regulation of Tissue Remodeling during Tooth Eruption

2021 ◽  
Vol 9 (1) ◽  
pp. 7
Author(s):  
Yusuke Makino ◽  
Kaoru Fujikawa ◽  
Miwako Matsuki-Fukushima ◽  
Satoshi Inoue ◽  
Masanori Nakamura
Keyword(s):  
Bacterial Infections ◽  
Tooth Movement ◽  
Tooth Eruption ◽  
Intercellular Adhesion Molecule ◽  
Enamel Organ ◽  
Pcr Analysis ◽  
Maturation Stage ◽  
Oral Epithelium ◽  
Rt Pcr ◽  
Inflammatory Reactions

Tooth eruption is characterized by a coordinated complex cascade of cellular and molecular events that promote tooth movement through the eruptive pathway. During tooth eruption, the stratum intermedium structurally changes to the papillary layer with tooth organ development. We previously reported intercellular adhesion molecule-1 (ICAM-1) expression on the papillary layer, which is the origin of the ICAM-1-positive junctional epithelium. ICAM-1 expression is induced by proinflammatory cytokines, including interleukin-1 and tumor necrosis factor. Inflammatory reactions induce tissue degradation. Therefore, this study aimed to examine whether inflammatory reactions are involved in tooth eruption. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed sequential expression of hypoxia-induced factor-1α, interleukin-1β, and chemotactic factors, including keratinocyte-derived chemokine (KC) and macrophage inflammatory protein-2 (MIP-2), during tooth eruption. Consistent with the RT-PCR results, immunohistochemical analysis revealed KC and MIP-2 expression in the papillary layer cells of the enamel organ from the ameloblast maturation stage. Moreover, there was massive macrophage and neutrophil infiltration in the connective tissue between the tooth organ and oral epithelium during tooth eruption. These findings suggest that inflammatory reactions might be involved in the degradation of tissue overlying the tooth organ. Further, these reactions might be induced by hypoxia in the tissue overlying the tooth organ, which results from decreased capillaries in the tissue. Our findings indicate that bacterial infections are not associated with the eruption process. Therefore, tooth eruption might be regulated by innate inflammatory mechanisms.

Neutrophil-dependent augmentation of PAF-induced vasoconstriction and albumin flux in coronary arterioles

1998 ◽  
Vol 275 (4) ◽  
pp. H1138-H1147 ◽  
Author(s):  
Qiaobing Huang ◽  
Mac Wu ◽  
Cynthia Meininger ◽  
Katherine Kelly ◽  
Yuan Yuan
Keyword(s):  
Platelet Activating Factor ◽  
Microvascular Dysfunction ◽  
Low Flow ◽  
Intercellular Adhesion Molecule ◽  
Neutrophil Adhesion ◽  
Intercellular Adhesion Molecule 1 ◽  
Apparent Permeability ◽  
Inflammatory Reactions ◽  
Coronary Arterioles ◽  
Flow Velocities

Platelet-activating factor (PAF) has been implicated in the pathogenesis of ischemic heart disease, reperfusion injury, and inflammatory reactions. Although neutrophils have been shown to primarily mediate PAF-induced microvascular dysfunction, the vasoactive effect of PAF and its neutrophil-dependent mechanism have not been directly and systematically studied in coronary resistance vessels. Therefore, the aim of this study was to examine the effects of PAF on coronary arteriolar function and neutrophil dynamics using an isolated and perfused microvessel preparation. Topical application of PAF to the vessels induced a dose-dependent decrease in the diameter but an increase in the apparent permeability coefficient of albumin. Disruption of the endothelium abolished the vasomotor response to PAF, and perfusion of neutrophils significantly augmented PAF-induced changes in vasomotor tone and permeability. Furthermore, the interaction between neutrophils and the endothelium was studied in the intact perfused coronary arterioles. Under control conditions, there were no adherent neutrophils observed in the vessels at varied intraluminal flow velocities. However, administration of PAF caused neutrophil adhesion to the endothelium of coronary arterioles at low flow velocities. Western blot analysis indicated that PAF upregulated the expression of intercellular adhesion molecule-1 in cultured coronary microvascular endothelial cells. Taken together, the results suggest that 1) PAF induces vasoconstriction and hyperpermeability in coronary arterioles via an endothelium-dependent and neutrophil-mediated mechanism, and 2) PAF is able to stimulate neutrophil adhesion in coronary arterioles under a condition of low flow rate.

scholarly journals The evidence of porcine hemagglutinating encephalomyelitis virus induced nonsuppurative encephalitis as the cause of death in piglets

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2443 ◽  
Author(s):  
Zi Li ◽  
Wenqi He ◽  
Yungang Lan ◽  
Kui Zhao ◽  
Xiaoling Lv ◽  
...  
Keyword(s):  
Nervous System ◽  
Cause Of Death ◽  
Viral Infections ◽  
Vaccine Development ◽  
Wild Strain ◽  
Effective Vaccine ◽  
Symptoms Of Depression ◽  
Encephalomyelitis Virus ◽  
Cns Dysfunction ◽  
Porcine Hemagglutinating Encephalomyelitis Virus

An acute outbreak of porcine hemagglutinating encephalomyelitis virus (PHEV) infection in piglets, characterized with neurological symptoms, vomiting, diarrhea, and wasting, occurred in China. Coronavirus-like particles were observed in the homogenized tissue suspensions of the brain of dead piglets by electron microscopy, and a wild PHEV strain was isolated, characterized, and designated as PHEV-CC14. Histopathologic examinations of the dead piglets showed characteristics of non-suppurative encephalitis, and some neurons in the cerebral cortex were degenerated and necrotic, and neuronophagia. Similarly, mice inoculated with PHEV-CC14 were found to have central nervous system (CNS) dysfunction, with symptoms of depression, arched waists, standing and vellicating front claws. Furthmore, PHEV-positive labeling of neurons in cortices of dead piglets and infected mice supported the viral infections of the nervous system. Then, the major structural genes of PHEV-CC14 were sequenced and phylogenetically analyzed, and the strain shared 95%–99.2% nt identity with the other PHEV strains available in GenBank. Phylogenetic analysis clearly proved that the wild strain clustered into a subclass with a HEV-JT06 strain. These findings suggested that the virus had a strong tropism for CNS, in this way, inducing nonsuppurative encephalitis as the cause of death in piglets. Simultaneously, the predicted risk of widespread transmission showed a certain variation among the PHEV strains currently circulating around the world. Above all, the information presented in this study can not only provide good reference for the experimental diagnosis of PHEV infection for pig breeding, but also promote its new effective vaccine development.

scholarly journals Monocytes in Neonatal Bacterial Sepsis: Think Tank or Workhorse?

BioChem ◽  
2022 ◽  
Vol 2 (1) ◽  
pp. 27-43
Author(s):  
Caitlin Doughty ◽  
Louise Oppermann ◽  
Niels-Ulrik Hartmann ◽  
Stephan Dreschers ◽  
Christian Gille ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Bacterial Infections ◽  
Cell Activation ◽  
Viral Infections ◽  
Organ Damage ◽  
Host Responses ◽  
Critical Event ◽  
Think Tank ◽  
Inflammatory Reactions ◽  
Inflammatory Conditions

Infection and sepsis remain among the leading causes of neonatal mortality. The susceptibility of newborns to infection can be attributed to their immature immune system. Regarding immune response, monocytes represent a numerically minor population of leukocytes. However, they contribute to a variety of immunological demands, such as continuous replenishment of resident macrophages under non-infectious conditions and migration to inflamed sites where they neutralize pathogens and secrete cytokines. Further functions include the presentation of antigens and T-cell activation. Cytokines coordinate host responses to bacterial and viral infections and orchestrate ongoing physiological signaling between cells of non-immune tissues. A critical event is the skewing of the cytokine repertoire to achieve a resolution of infection. In this regard, monocytes may hold a key position as deciders in addition to their phagocytic activity, securing the extinction of pathogens to prevent broader organ damage by toxins and pro-inflammatory reactions. Neonatal monocytes undergo various regulatory and metabolic changes. Thus, they are thought to be vulnerable in anticipating pro-inflammatory conditions and cause severe progressions which increase the risk of developing sepsis. Furthermore, clinical studies have shown that exposure to inflammation puts neonates at a high risk for adverse pulmonary, immunological and other organ developments, which may result in multiorgan disease. This review discusses significant functions and impairments of neonatal monocytes that are decisive for the outcome of bacterial infections.

scholarly journals Improving the therapy of generalized forms of Meningococcal infection in children using extracorporeal hemocorrection

2021 ◽  
Vol 20 (2) ◽  
pp. 49-56
Author(s):  
K. V. Markova ◽  
E. Yu. Skripchenko ◽  
K. V. Serednyakov ◽  
Yu. V. Lobzin ◽  
N. V. Skripchenko ◽  
...  
Keyword(s):  
Septic Shock ◽  
Multiple Organ Failure ◽  
Organ Failure ◽  
Multiple Organ ◽  
Meningococcal Infection ◽  
Basic Drug ◽  
Inflammatory Reactions ◽  
Clinical Center ◽  
Refractory Septic Shock ◽  
Group 2

Invasive meningococcal infection is a significant cause of death, reaching 80% in septic shock. The Pediatric Research and Clinical Center for Infectious Diseases (PRCCID) has developed an algorithm for the treatment of children with invasive meningococcal infection with refractory septic shock and multiple organ failure syndrome, which includes basic drug therapy with polymyxin hemoperfusion in combination with extended methods of extracorporeal hemocorrection.Purpose: to evaluate the effectiveness of extracorporeal hemocorrection operations in children with invasive meningococcal infection with refractory septic shock and multiple organ failure syndrome.Materials and research methods: to the intensive care unit of the PRCCID for the analyzed period 2006—2020 34 children were hospitalized with invasive meningococcal infection with refractory septic shock and multiple organ failure syndrome. Two groups were formed: Group 1 — children admitted to the PRCCID in the period 2014—2020 (n = 23), who underwent polymyxin hemoperfusion simultaneously with extended methods of extracorporeal hemocorrection, group 2 — children hospitalized in 2006—201 3 (n = 1 1), methods of extracorporeal hemocorrection were not performed. The Mann-Whitney U-test and ANOVA were used to evaluate the results.Results and discussion: the use of extracorporeal hemocorrection operations in the complex therapy of invasive forms of meningococcal infection with refractory septic shock and multiple organ failure syndrome in children provides stabilization of central hemodynamics, reduces clinical and laboratory inflammatory reactions, helps to reduce the dose of vasopressor drugs and parameters of respiratory support, and also increases patient survival rate by 82.6%.

Monocyte-Independent and -Dependent Regulation of Regulatory T-Cell Development in Mycoplasma Infection

2020 ◽  
Author(s):  
Ryo Takahashi ◽  
Tetsuo Shiohara ◽  
Yoshiko Mizukawa
Keyword(s):  
Th17 Cells ◽  
Viral Infections ◽  
T Cell Development ◽  
Allergic Diseases ◽  
Acute Stage ◽  
Dependent Manner ◽  
Virus Infections ◽  
Treg Function ◽  
Toll Like Receptor 2 ◽  
And Function

Abstract Background Although Mycoplasma pneumoniae (MP) infection has been implicated in the pathogenesis of allergic diseases, the mechanism of this trigger remains unknown. We explored the mechanism for how MP infection could tilt the balance between regulatory T cells (Tregs) and Th17 cells. Methods We analyzed the frequency, phenotype, and function of Tregs in patients at the different stages of MP and various virus infections over a period of more than 1 year. We examined the effect of monocytes to elucidate signals that can regulate the balance between Treg and Th17 cells. Results The functional activity of Tregs was profoundly impaired during the acute stage of MP as well as viral infections. Upon resolution, however, the Treg function remained impaired even 1 year after MP infection. In the resolution stage, the impaired Treg function was associated with an increase in interleukin (IL) 17A+ Tregs and Th17 cells. Development of Th17 cells was dependent on the “aberrant” proinflammatory monocytes (pMOs), characterized by potent ability to produce IL-6 in a Toll-like receptor 2–dependent manner. Conclusions Depending on the prevalence of the pMOs, Tregs and Th17 cells could mutually regulate the number and function of the other. The pMOs/IL-6 could be crucial therapeutic targets against MP-induced allergic diseases.

scholarly journals Extracellular Vesicles in the Pathogenesis of Viral Infections in Humans

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1200 ◽  
Author(s):  
Allen Caobi ◽  
Madhavan Nair ◽  
Andrea D. Raymond
Keyword(s):  
Extracellular Vesicles ◽  
Viral Infections ◽  
Membrane Vesicles ◽  
Response Modulation ◽  
Viral Spread ◽  
Neurotropic Viruses ◽  
Immunodeficiency Virus ◽  
Immune Response Modulation ◽  
Potential Use

Most cells can release extracellular vesicles (EVs), membrane vesicles containing various proteins, nucleic acids, enzymes, and signaling molecules. The exchange of EVs between cells facilitates intercellular communication, amplification of cellular responses, immune response modulation, and perhaps alterations in viral pathogenicity. EVs serve a dual role in inhibiting or enhancing viral infection and pathogenesis. This review examines the current literature on EVs to explore the complex role of EVs in the enhancement, inhibition, and potential use as a nanotherapeutic against clinically relevant viruses, focusing on neurotropic viruses: Zika virus (ZIKV) and human immunodeficiency virus (HIV). Overall, this review’s scope will elaborate on EV-based mechanisms, which impact viral pathogenicity, facilitate viral spread, and modulate antiviral immune responses.

scholarly journals Cigarette Smoke Condensate Exposure Changes RNA Content of Extracellular Vesicles Released from Small Airway Epithelial Cells

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1652
Author(s):  
Tiziana Corsello ◽  
Andrzej S. Kudlicki ◽  
Roberto P. Garofalo ◽  
Antonella Casola
Keyword(s):  
Epithelial Cells ◽  
Cigarette Smoke ◽  
Extracellular Vesicles ◽  
Viral Infections ◽  
Cell Communication ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Cigarette Smoke Condensate ◽  
Diverse Range ◽  
Chronic Lung Diseases

Exposure to environmental tobacco smoke (ETS) is a known risk factor for the development of chronic lung diseases, cancer, and the exacerbation of viral infections. Extracellular vesicles (EVs) have been identified as novel mediators of cell–cell communication through the release of biological content. Few studies have investigated the composition/function of EVs derived from human airway epithelial cells (AECs) exposed to cigarette smoke condensate (CSC), as surrogates for ETS. Using novel high-throughput technologies, we identified a diverse range of small noncoding RNAs (sncRNAs), including microRNA (miRNAs), Piwi-interacting RNA (piRNAs), and transfer RNA (tRNAs) in EVs from control and CSC-treated SAE cells. CSC treatment resulted in significant changes in the EV content of miRNAs. A total of 289 miRNAs were identified, with five being significantly upregulated and three downregulated in CSC EVs. A total of 62 piRNAs were also detected in our EV preparations, with five significantly downregulated and two upregulated in CSC EVs. We used TargetScan and Gene Ontology (GO) analysis to predict the biological targets of hsa-miR-3913-5p, the most represented miRNA in CSC EVs. Understanding fingerprint molecules in EVs will increase our knowledge of the relationship between ETS exposure and lung disease, and might identify potential molecular targets for future treatments.

scholarly journals Unraveling Sugar Binding Modes to DC-SIGN by Employing Fluorinated Carbohydrates

Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2337 ◽  
Author(s):  
J. Daniel Martínez ◽  
Pablo Valverde ◽  
Sandra Delgado ◽  
Cecilia Romanò ◽  
Bruno Linclau ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Viral Infections ◽  
Md Simulations ◽  
Binding Mode ◽  
Intercellular Adhesion Molecule ◽  
Binding Modes ◽  
Binding Epitope ◽  
First Time ◽  
Biomedical Interest ◽  
Specific Sugar

A fluorine nuclear magnetic resonance (19F-NMR)-based method is employed to assess the binding preferences and interaction details of a library of synthetic fluorinated monosaccharides towards dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN), a lectin of biomedical interest, which is involved in different viral infections, including HIV and Ebola, and is able to recognize a variety of self- and non-self-glycans. The strategy employed allows not only screening of a mixture of compounds, but also obtaining valuable information on the specific sugar–protein interactions. The analysis of the data demonstrates that monosaccharides Fuc, Man, Glc, and Gal are able to bind DC-SIGN, although with decreasing affinity. Moreover, a new binding mode between Man moieties and DC-SIGN, which might have biological implications, is also detected for the first time. The combination of the 19F with standard proton saturation transfer difference (1H-STD-NMR) data, assisted by molecular dynamics (MD) simulations, permits us to successfully define this new binding epitope, where Man coordinates a Ca2+ ion of the lectin carbohydrate recognition domain (CRD) through the axial OH-2 and equatorial OH-3 groups, thus mimicking the Fuc/DC-SIGN binding architecture.

Sign in / Sign up

Export Citation Format

Share Document