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1.
Molecules ; 26(17)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34500777

RESUMO

Human neutrophil elastase (HNE) is a uniquely destructive serine protease with the ability to unleash a wave of proteolytic activity by destroying the inhibitors of other proteases. Although this phenomenon forms an important part of the innate immune response to invading pathogens, it is responsible for the collateral host tissue damage observed in chronic conditions such as chronic obstructive pulmonary disease (COPD), and in more acute disorders such as the lung injuries associated with COVID-19 infection. Previously, a combinatorially selected activity-based probe revealed an unexpected substrate preference for oxidised methionine, which suggests a link to oxidative pathogen clearance by neutrophils. Here we use oxidised model substrates and inhibitors to confirm this observation and to show that neutrophil elastase is specifically selective for the di-oxygenated methionine sulfone rather than the mono-oxygenated methionine sulfoxide. We also posit a critical role for ordered solvent in the mechanism of HNE discrimination between the two oxidised forms methionine residue. Preference for the sulfone form of oxidised methionine is especially significant. While both host and pathogens have the ability to reduce methionine sulfoxide back to methionine, a biological pathway to reduce methionine sulfone is not known. Taken together, these data suggest that the oxidative activity of neutrophils may create rapidly cleaved elastase "super substrates" that directly damage tissue, while initiating a cycle of neutrophil oxidation that increases elastase tissue damage and further neutrophil recruitment.


Assuntos
Imunidade Inata , Elastase de Leucócito/metabolismo , Metionina/análogos & derivados , Neutrófilos/imunologia , Biocatálise , COVID-19/imunologia , COVID-19/patologia , COVID-19/virologia , Domínio Catalítico/genética , Ensaios Enzimáticos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Elastase de Leucócito/antagonistas & inibidores , Elastase de Leucócito/genética , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Metionina/metabolismo , Simulação de Dinâmica Molecular , Infiltração de Neutrófilos , Neutrófilos/enzimologia , Oxirredução/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/patologia , SARS-CoV-2/imunologia , Especificidade por Substrato/imunologia
2.
Int J Mol Sci ; 22(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34502134

RESUMO

The current spreading coronavirus SARS-CoV-2 is highly infectious and pathogenic. In this study, we screened the gene expression of three host receptors (ACE2, DC-SIGN and L-SIGN) of SARS coronaviruses and dendritic cells (DCs) status in bulk and single cell transcriptomic datasets of upper airway, lung or blood of COVID-19 patients and healthy controls. In COVID-19 patients, DC-SIGN gene expression was interestingly decreased in lung DCs but increased in blood DCs. Within DCs, conventional DCs (cDCs) were depleted while plasmacytoid DCs (pDCs) were augmented in the lungs of mild COVID-19. In severe cases, we identified augmented types of immature DCs (CD22+ or ANXA1+ DCs) with MHCII downregulation. In this study, our observation indicates that DCs in severe cases stimulate innate immune responses but fail to specifically present SARS-CoV-2. It provides insights into the profound modulation of DC function in severe COVID-19.


Assuntos
COVID-19/imunologia , Moléculas de Adesão Celular/genética , Células Dendríticas/imunologia , Regulação da Expressão Gênica/imunologia , Lectinas Tipo C/genética , Receptores de Superfície Celular/genética , SARS-CoV-2/imunologia , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/diagnóstico , COVID-19/patologia , COVID-19/virologia , Moléculas de Adesão Celular/metabolismo , Conjuntos de Dados como Assunto , Células Dendríticas/metabolismo , Estudo de Associação Genômica Ampla , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Lectinas Tipo C/metabolismo , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Análise da Randomização Mendeliana , Nasofaringe/imunologia , Nasofaringe/patologia , Nasofaringe/virologia , RNA-Seq , Receptores de Superfície Celular/metabolismo , Índice de Gravidade de Doença , Análise de Célula Única
3.
Sci Immunol ; 6(62)2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376481

RESUMO

To understand how a protective immune response against SARS-CoV-2 develops over time, we integrated phenotypic, transcriptional and repertoire analyses on PBMCs from mild and severe COVID-19 patients during and after infection, and compared them to healthy donors (HD). A type I IFN-response signature marked all the immune populations from severe patients during the infection. Humoral immunity was dominated by IgG production primarily against the RBD and N proteins, with neutralizing antibody titers increasing post infection and with disease severity. Memory B cells, including an atypical FCRL5+ T-BET+ memory subset, increased during the infection, especially in patients with mild disease. A significant reduction of effector memory, CD8+ T cells frequency characterized patients with severe disease. Despite such impairment, we observed robust clonal expansion of CD8+ T lymphocytes, while CD4+ T cells were less expanded and skewed toward TCM and TH2-like phenotypes. MAIT cells were also expanded, but only in patients with mild disease. Terminally differentiated CD8+ GZMB+ effector cells were clonally expanded both during the infection and post-infection, while CD8+ GZMK+ lymphocytes were more expanded post-infection and represented bona fide memory precursor effector cells. TCR repertoire analysis revealed that only highly proliferating T cell clonotypes, which included SARS-CoV-2-specific cells, were maintained post-infection and shared between the CD8+ GZMB+ and GZMK+ subsets. Overall, this study describes the development of immunity against SARS-CoV-2 and identifies an effector CD8+ T cell population with memory precursor-like features.


Assuntos
COVID-19/genética , COVID-19/imunologia , Interações Hospedeiro-Patógeno/imunologia , Imunofenotipagem , SARS-CoV-2/imunologia , Transcriptoma , Adulto , Idoso , Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Biomarcadores , COVID-19/virologia , Plasticidade Celular/genética , Plasticidade Celular/imunologia , Evolução Clonal/imunologia , Feminino , Perfilação da Expressão Gênica , Humanos , Isotipos de Imunoglobulinas/imunologia , Memória Imunológica , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
4.
Blood Cancer J ; 11(8): 142, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376633

RESUMO

This study evaluated the safety and immunogenicity of BNT162b2 vaccine in patients with hematological malignancies. Antibodies blocking spike binding to immobilized ACE-2 (NAb) correlated with anti-Spike (S) IgG d42 titers (Spearman r = 0.865, p < 0.0001), and an anti-S IgG d42 level ≥3100 UA/mL was predictive of NAb ≥ 30%, the positivity cutoff for NAb (p < 0.0001). Only 47% of the patients achieved an anti-S IgG d42 level ≥3100 UA/mL after the two BNT162b2 inocula, compared to 87% of healthy controls. In multivariable analysis, male patients, use of B-cell targeting treatment within the last 12 months prior to vaccination, and CD19+ B-cell level <120/uL, were associated with a significantly decreased probability of achieving a protective anti-S IgG level after the second BNT162b2 inoculum. Finally, using the IFN-γ ELISPOT assay, we found a significant increase in T-cell response against the S protein, with 53% of patients having an anti-S IgG-positive ELISPOT after the second BNT162b2 inoculum. There was a correlation between the anti-S ELISPOT response and IgG d42 level (Spearman r = 0.3026, p = 0.012). These findings suggest that vaccination with two BNT162b2 inocula translates into a significant increase in humoral and cellular response in patients with hematological malignancies, but only around half of the patients can likely achieve effective immune protection against COVID-19.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/complicações , COVID-19/imunologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/imunologia , Imunogenicidade da Vacina , SARS-CoV-2/imunologia , Imunidade Adaptativa , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Vacinas contra COVID-19/administração & dosagem , Comorbidade , Feminino , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Linfócitos T/imunologia , Linfócitos T/metabolismo , Adulto Jovem
5.
Int J Med Sci ; 18(14): 3236-3248, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34400893

RESUMO

Natural killer cells, one of the important types of innate immune cells, play a pivotal role in the antiviral process in vivo. It has been shown that increasing NK cell activity may promote the alleviation of viral infections, even severe infection-induced sepsis. Given the current state of the novel coronavirus (SARS-CoV-2) global pandemic, clarifying the anti-viral function of NK cells would be helpful for revealing the mechanism of host immune responses and decipher the progression of COVID-19 and providing important clues for combating this pandemic. In this review, we summarize the roles of NK cells in viral infection and sepsis as well as the potential possibilities of NK cell-based immunotherapy for treating COVID-19.


Assuntos
COVID-19/imunologia , Interações Hospedeiro-Patógeno/imunologia , Células Matadoras Naturais/fisiologia , Sepse/imunologia , COVID-19/terapia , Humanos , Imunoterapia , SARS-CoV-2 , Sepse/virologia
6.
Viruses ; 13(7)2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34372572

RESUMO

Human APOBEC3 (apolipoprotein B mRNA-editing catalytic polypeptide-like 3) enzymes are capable of inhibiting a wide range of endogenous and exogenous viruses using deaminase and deaminase-independent mechanisms. These enzymes are essential components of our innate immune system, as evidenced by (a) their strong positive selection and expansion in primates, (b) the evolution of viral counter-defense mechanisms, such as proteasomal degradation mediated by HIV Vif, and (c) hypermutation and inactivation of a large number of integrated HIV-1 proviruses. Numerous APOBEC3 single nucleotide polymorphisms, haplotypes, and splice variants have been identified in humans. Several of these variants have been reported to be associated with differential antiviral immunity. This review focuses on the current knowledge in the field about these natural variations and their roles in infectious diseases.


Assuntos
Desaminases APOBEC/genética , Desaminases APOBEC/metabolismo , Viroses/genética , Citidina Desaminase/genética , Citosina Desaminase/genética , HIV-1/fisiologia , Vírus da Hepatite B/fisiologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata/imunologia , Polimorfismo Genético/genética , Isoformas de Proteínas/genética , Viroses/metabolismo , Replicação Viral/genética
8.
mSphere ; 6(4): e0064721, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34378982

RESUMO

Basigin, or CD147, has been reported as a coreceptor used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to invade host cells. Basigin also has a well-established role in Plasmodium falciparum malaria infection of human erythrocytes, where it is bound by one of the parasite's invasion ligands, reticulocyte binding protein homolog 5 (RH5). Here, we sought to validate the claim that the receptor binding domain (RBD) of SARS-CoV-2 spike glycoprotein can form a complex with basigin, using RH5-basigin as a positive control. Using recombinantly expressed proteins, size exclusion chromatography and surface plasmon resonance, we show that neither RBD nor full-length spike glycoprotein bind to recombinant human basigin (expressed in either Escherichia coli or mammalian cells). Further, polyclonal anti-basigin IgG did not block SARS-CoV-2 infection of Vero E6 cells. Given the immense interest in SARS-CoV-2 therapeutic targets to improve treatment options for those who become seriously ill with coronavirus disease 2019 (COVID-19), we would caution the inclusion of basigin in this list on the basis of its reported direct interaction with SARS-CoV-2 spike glycoprotein. IMPORTANCE Reducing the mortality and morbidity associated with COVID-19 remains a global health priority. Vaccines have proven highly effective at preventing infection and hospitalization, but efforts must continue to improve treatment options for those who still become seriously ill. Critical to these efforts is the identification of host factors that are essential to viral entry and replication. Basigin, or CD147, was previously identified as a possible therapeutic target based on the observation that it may act as a coreceptor for SARS-CoV-2, binding to the receptor binding domain of the spike protein. Here, we show that there is no direct interaction between the RBD and basigin, casting doubt on its role as a coreceptor and plausibility as a therapeutic target.


Assuntos
Basigina/metabolismo , COVID-19/metabolismo , COVID-19/virologia , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Animais , Basigina/imunologia , COVID-19/imunologia , Linhagem Celular , Chlorocebus aethiops , Interações Hospedeiro-Patógeno/imunologia , Humanos , Ligação Proteica/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Células Vero , Internalização do Vírus
9.
Nat Commun ; 12(1): 4882, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385466

RESUMO

Genetic variants of the interferon lambda (IFNL) gene locus are strongly associated with spontaneous and IFN treatment-induced clearance of hepatitis C virus (HCV) infections. Individuals with the ancestral IFNL4-dG allele are not able to clear HCV in the acute phase and have more than a 90% probability to develop chronic hepatitis C (CHC). Paradoxically, the IFNL4-dG allele encodes a fully functional IFNλ4 protein with antiviral activity against HCV. Here we describe an effect of IFNλ4 on HCV antigen presentation. Only minor amounts of IFNλ4 are secreted, because the protein is largely retained in the endoplasmic reticulum (ER) where it induces ER stress. Stressed cells are significantly weaker activators of HCV specific CD8+ T cells than unstressed cells. This is not due to reduced MHC I surface presentation or extracellular IFNλ4 effects, since T cell responses are restored by exogenous loading of MHC with HCV antigens. Rather, IFNλ4 induced ER stress impairs HCV antigen processing and/or loading onto the MHC I complex. Our results provide a potential explanation for the IFNλ4-HCV paradox.


Assuntos
Apresentação do Antígeno/imunologia , Linfócitos T CD8-Positivos/imunologia , Hepacivirus/imunologia , Interleucinas/imunologia , Ativação Linfocitária/imunologia , Células A549 , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/virologia , Linhagem Celular Tumoral , Regulação da Expressão Gênica/imunologia , Genótipo , Células Hep G2 , Hepacivirus/genética , Hepacivirus/fisiologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Interleucinas/genética , Interleucinas/metabolismo
10.
Immunology ; 164(1): 1-2, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34382228

RESUMO

Mass vaccination of the global population against SARS-CoV-2 will, we hope, turn the tide against this devastating pandemic. To complement vaccinations, better tools are needed to enable viral infections and immunological protection to be monitored. Accurate tools provide sound data for informed decision-making at many levels, from personal to governmental. The measurement of viral RNA is currently routinely used to detect active infections, but only gives a positive result during infection and is unable to reveal historic infections. Tests involving a detection of SARS-CoV-2-specific antibodies can reveal prior exposures to virus and can measure anti-viral immune responses induced after natural infection or after vaccination. They may eventually also be used to predict an individual's likelihood of becoming re-infected. Here, we report on the development of a sensitive ELISA technique to detect multiple isotypes of antibodies against the spike glycoprotein, in samples of both serum and saliva. This paper provides an important step towards understanding the immune response to SARS-CoV-2 and may therefore eventually help us to effectively control it.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/virologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Anticorpos Antivirais/sangue , Especificidade de Anticorpos , COVID-19/sangue , COVID-19/diagnóstico , Suscetibilidade a Doenças , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/normas , Interações Hospedeiro-Patógeno/imunologia , Humanos , Biópsia Líquida , Sensibilidade e Especificidade , Carga Viral
11.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445148

RESUMO

The gram-positive pathogenic bacterium Clavibacter michiganensis subsp. michiganensis (Cmm) causes bacterial canker disease in tomato, affecting crop yield and fruit quality. To understand how tomato plants respond, the dynamic expression profile of host genes was analyzed upon Cmm infection. Symptoms of bacterial canker became evident from the third day. As the disease progressed, the bacterial population increased in planta, reaching the highest level at six days and remained constant till the twelfth day post inoculation. These two time points were selected for transcriptomics. A progressive down-regulation of key genes encoding for components of the photosynthetic apparatus was observed. Two temporally separated defense responses were observed, which were to an extent interdependent. During the primary response, genes of the phenylpropanoid pathway were diverted towards the synthesis of monolignols away from S-lignin. In dicots, lignin polymers mainly consist of G- and S-units, playing an important role in defense. The twist towards G-lignin enrichment is consistent with previous findings, highlighting a response to generate an early protective barrier and to achieve a tight interplay between lignin recomposition and the primary defense response mechanism. Upon progression of Cmm infection, the temporal deactivation of phenylpropanoids coincided with the upregulation of genes that belong in a secondary response mechanism, supporting an elegant reprogramming of the host transcriptome to establish a robust defense apparatus and suppress pathogen invasion. This high-throughput analysis reveals a dynamic reorganization of plant defense mechanisms upon bacterial infection to implement an array of barriers preventing pathogen invasion and spread.


Assuntos
Regulação para Baixo/genética , Lycopersicon esculentum/genética , Lycopersicon esculentum/microbiologia , Fotossíntese/genética , Imunidade Vegetal/genética , Imunidade Vegetal/imunologia , Clavibacter/genética , Infecções por Bactérias Gram-Positivas/genética , Infecções por Bactérias Gram-Positivas/imunologia , Infecções por Bactérias Gram-Positivas/microbiologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Fotossíntese/imunologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Transcriptoma/genética , Regulação para Cima/genética
12.
J Insect Sci ; 21(4)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34314494

RESUMO

The use of Galleria mellonella (Linnaeus) (Lepidoptera: Pyralidae), an economical insect model, for the study of enteropathogenic Escherichia coli (Migula) (EPEC), a diarrheagenic human pathogen, has been demonstrated previously but remains poorly understood. The present study characterizes the Galleria-EPEC system extensively for future studies using this system. We found that EPEC causes disease in G. mellonella larvae when injected intrahemocoelically but not orally. Disease manifests as increased mortality, decreased survival time, delayed pupation, decreased pupal mass, increased pupal duration, and hemocytopenia. Disease symptoms are dose-dependent and can be used as metrics for measuring EPEC virulence in future studies. The type III secretion system was only partially responsible for EPEC virulence in G. mellonella while the majority of the virulence remains unknown in origin. EPEC elicits insect anti-bacterial immune responses including melanization, hemolymph coagulation, nodulation, and phagocytosis. The immune responses were unable to control EPEC replication in the early stage of infection (≤3 h post-injection). EPEC clearance from the hemocoel does not guarantee insect survival. Overall, this study provided insights into EPEC virulence and pathogenesis in G. mellonella and identified areas of future research using this system.


Assuntos
Modelos Animais de Doenças , Escherichia coli Enteropatogênica/patogenicidade , Infecções por Escherichia coli/imunologia , Interações Hospedeiro-Patógeno/imunologia , Mariposas/imunologia , Animais , Infecções por Escherichia coli/mortalidade , Feminino , Larva/imunologia , Masculino
13.
Front Immunol ; 12: 660632, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305892

RESUMO

The novel SARS-CoV-2virus that caused the disease COVID-19 is currently a pandemic worldwide. The virus requires an alveolar type-2 pneumocyte in the host to initiate its life cycle. The viral S1 spike protein helps in the attachment of the virus on toACE-2 receptors present on type-2 pneumocytes, and the S2 spike protein helps in the fusion of the viral membrane with the host membrane. Fusion of the SARS-CoV-2virus and host membrane is followed by entry of viral RNA into the host cells which is directly translated into the replicase-transcriptase complex (RTC) following viral RNA and structural protein syntheses. As the virus replicates within type-2 pneumocytes, the host immune system is activated and alveolar macrophages start secreting cytokines and chemokines, acting as an inflammatory mediator, and chemotactic neutrophils, monocytes, natural NK cells, and CD8+ T cells initiate the local phagocytosis of infected cells. It is not the virus that kills COVID-19 patients; instead, the aberrant host immune response kills them. Modifying the response from the host immune system could reduce the high mortality due to SARS-CoV-2 infection. The present study examines the viral life cycle intype-2 pneumocytes and resultant host immune response along with possible therapeutic targets.


Assuntos
COVID-19/imunologia , COVID-19/terapia , Imunomodulação , SARS-CoV-2/patogenicidade , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Células Epiteliais Alveolares/virologia , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/patologia , COVID-19/virologia , Citocinas/imunologia , Citocinas/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , SARS-CoV-2/fisiologia
14.
PLoS One ; 16(7): e0253551, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34310603

RESUMO

BACKGROUND: The novel coronavirus SARS-CoV2 that causes COVID-19 has resulted in the death of more than 2.5 million people, but no cure exists. Although passive immunization with COVID-19 convalescent plasma (CCP) provides a safe and viable therapeutic option, the selection of optimal units for therapy in a timely fashion remains a barrier. STUDY DESIGN AND METHODS: Since virus neutralization is a necessary characteristic of plasma that can benefit recipients, the neutralizing titers of plasma samples were measured using a retroviral-pseudotype assay. Binding antibody titers to the spike (S) protein were also determined by a clinically available serological assay (Ortho-Vitros total IG), and an in-house ELISA. The results of these assays were compared to a measurement of antibodies directed to the receptor binding domain (RBD) of the SARS-CoV2 S protein (Promega Lumit Dx). RESULTS: All measures of antibodies were highly variable, but correlated, to different degrees, with each other. However, the anti-RBD antibodies correlated with viral neutralizing titers to a greater extent than the other antibody assays. DISCUSSION: Our observations support the use of an anti-RBD assay such as the Lumit Dx assay, as an optimal predictor of the neutralization capability of CCP.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/terapia , Imunoglobulina G/sangue , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/imunologia , Doadores de Sangue , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/virologia , Ensaio de Imunoadsorção Enzimática , Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Soros Imunes/química , Imunização Passiva/métodos , Testes de Neutralização , Valor Preditivo dos Testes , Ligação Proteica , Domínios Proteicos , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Glicoproteína da Espícula de Coronavírus/imunologia
16.
Int J Mol Sci ; 22(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204438

RESUMO

Hepatitis C virus (HCV) is associated with various liver diseases. Chronic HCV infection is characterized by an abnormal host immune response. Therefore, it is speculated that to suppress HCV, a well-regulated host immune response is necessary. 2-O-methylhonokiol was identified by the screening of anti-HCV compounds using Renilla luciferase assay in Huh 7.5/Con 1 genotype 1b replicon cells. Here, we investigated the mechanism by which 2-O-methylhonokiol treatment inhibits HCV replication using real-time PCR. Our data shows that treatment with 2-O-methylhonokiol activated innate immune responses via nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway. Additionally, the immunoprecipitation result shows that treatment with 2-O-methylhonokiol augmented tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) by preventing p62 from binding to TRAF6, resulting in reduced autophagy caused by HCV. Finally, we reproduced our data with the conditioned media from 2-O-methylhonokiol-treated cells. These findings strongly suggest that 2-O-methylhonokiol enhances the host immune response and suppresses HCV replication via TRAF6-mediated NF-kB activation.


Assuntos
Hepacivirus/fisiologia , Hepatite C/metabolismo , Hepatite C/virologia , Interações Hospedeiro-Patógeno , NF-kappa B/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Replicação Viral , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linhagem Celular , Células Cultivadas , Hepatite C/imunologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Modelos Biológicos , Estrutura Molecular
17.
NPJ Biofilms Microbiomes ; 7(1): 57, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34230496

RESUMO

Bacterial vaginosis (BV) is a gynecologic disorder characterized by a shift in cervicovaginal microbiota from Lactobacillus spp. dominance to a polymicrobial biofilm composed of diverse anaerobes. We utilized a well-characterized human three-dimensional cervical epithelial cell model in conjunction with untargeted metabolomics and immunoproteomics analyses to determine the immunometabolic contribution of three members of the Veillonellaceae family: Veillonella atypica, Veillonella montpellierensis and Megasphaera micronuciformis at this site. We found that Veillonella spp. infections induced significant elevation of polyamines. M. micronuciformis infections significantly increased soluble inflammatory mediators, induced moderate levels of cell cytotoxicity, and accumulation of cell membrane lipids relative to Veillonella spp. Notably, both V. atypica and V. montpellierensis infections resulted in consumption of lactate, a key metabolite linked to gynecologic and reproductive health. Collectively our approach and data provide unique insights into the specific contributions of Veillonellaceae members to the pathogenesis of BV and women's health.


Assuntos
Metabolismo Energético , Membrana Mucosa/metabolismo , Membrana Mucosa/microbiologia , Vagina/metabolismo , Vagina/microbiologia , Veillonellaceae/fisiologia , Aminoácidos/metabolismo , Técnicas de Cultura de Células , Biologia Computacional/métodos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Células Epiteliais/ultraestrutura , Feminino , Interações Hospedeiro-Patógeno/imunologia , Humanos , Metabolismo dos Lipídeos , Metaboloma , Metabolômica/métodos , Vaginose Bacteriana/metabolismo , Vaginose Bacteriana/microbiologia
18.
Int J Mol Sci ; 22(14)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34298992

RESUMO

Non-Hodgkin B-cell lymphomas (NHL) are a heterogeneous group of lymphoid neoplasms with complex etiopathology, rich symptomatology, and a variety of clinical courses, therefore requiring different therapeutic approaches. The hypothesis that an infectious agent may initiate chronic inflammation and facilitate B lymphocyte transformation and lymphogenesis has been raised in recent years. Viruses, like EBV, HTLV-1, HIV, HCV and parasites, like Plasmodium falciparum, have been linked to the development of lymphomas. The association of chronic Helicobacter pylori (H. pylori) infection with mucosa-associated lymphoid tissue (MALT) lymphoma, Borrelia burgdorferi with cutaneous MALT lymphoma and Chlamydophila psittaci with ocular adnexal MALT lymphoma is well documented. Recent studies have indicated that other infectious agents may also be relevant in B-cell lymphogenesis such as Coxiella burnettii, Campylobacter jejuni, Achromobacter xylosoxidans, and Escherichia coli. The aim of the present review is to provide a summary of the current literature on infectious bacterial agents associated with B-cell NHL and to discuss its role in lymphogenesis, taking into account the interaction between infectious agents, host factors, and the tumor environment.


Assuntos
Infecções Bacterianas/complicações , Linfoma de Burkitt/microbiologia , Infecções por Helicobacter/microbiologia , Interações Hospedeiro-Patógeno , Linfoma de Zona Marginal Tipo Células B/microbiologia , Linfoma Difuso de Grandes Células B/microbiologia , Infecções Bacterianas/imunologia , Linfoma de Burkitt/complicações , Linfoma de Burkitt/patologia , Carcinogênese/genética , Carcinogênese/imunologia , Carcinogênese/metabolismo , Infecções por Helicobacter/complicações , Helicobacter pylori/patogenicidade , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Linfoma de Zona Marginal Tipo Células B/complicações , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/patologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
19.
Viruses ; 13(6)2021 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-34199161

RESUMO

Interferon gamma (IFN-γ) is considered a key moderator of cell-mediated immunity. However, little is known about its association with granzyme B, which plays an important role in the effector function of cytotoxic T lymphocytes (CTLs). In the present study, we collected blood samples from 32 healthy adults before and after vaccination with inactivated influenza vaccine in 2017/18 to measure the levels of IFN-γ and granzyme B, which play roles in cell-mediated immunity, and hemagglutination inhibition (HAI) antibody, which plays a role in humoral immunity. The levels of IFN-γ and granzyme B were significantly correlated both before and after vaccination. Furthermore, the post-vaccine fold increases in the IFN-γ and granzyme B levels were significantly correlated. The levels of IFN-γ and granzyme B decreased five months after vaccination in more than half of the subjects who exhibited an increase in IFN-γ and granzyme B at two weeks post-vaccination. This is the first study to investigate the correlation between IFN-γ and granzyme B levels following influenza vaccination. Our study suggests that both IFN-γ and granzyme B can be used as markers of cell-mediated immunity.


Assuntos
Granzimas/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Imunidade Celular , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Influenza Humana/metabolismo , Interferon gama/metabolismo , Adulto , Feminino , Humanos , Influenza Humana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Vacinação
20.
Cells ; 10(6)2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208037

RESUMO

Neutrophils are the most abundant circulating innate immune cells and comprise the first immune defense line, as they are the most rapidly recruited cells at sites of infection or inflammation. Their main microbicidal mechanisms are degranulation, phagocytosis, cytokine secretion and the formation of extracellular traps. Neutrophil extracellular traps (NETs) are a microbicidal mechanism that involves neutrophil death. Since their discovery, in vitro and in vivo neutrophils have been challenged with a range of stimuli capable of inducing or inhibiting NET formation, with the objective to understand its function and regulation in health and disease. These networks composed of DNA and granular components are capable of immobilizing and killing pathogens. They comprise enzymes such as myeloperoxidase, elastase, cathepsin G, acid hydrolases and cationic peptides, all with antimicrobial and antifungal activity. Therefore, the excessive formation of NETs can also lead to tissue damage and promote local and systemic inflammation. Based on this concept, in this review, we focus on the role of NETs in different infectious and inflammatory diseases of the mucosal epithelia and skin.


Assuntos
Armadilhas Extracelulares/fisiologia , Membrana Mucosa/imunologia , Dermatopatias/imunologia , Células Epiteliais/imunologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata/fisiologia , Neutrófilos/imunologia , Neutrófilos/fisiologia , Dermatopatias/patologia
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