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1.
Science ; 370(6514): 294-295, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33060350
2.
Urol Clin North Am ; 47(4): 433-442, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008494

RESUMO

Natural killer (NK) cells are potently cytolytic innate lymphocytes involved in the immune surveillance of tumors and virally infected cells. Although much progress has been made in manipulating the ability of T cells to recognize and eliminate tumors, a comprehensive understanding of NK-cell infiltration into solid tumors, and their amenability to immunomodulation, remains incomplete. This article discusses recent studies showing that urologic tumors are infiltrated by NK cells and that these NK cells are often dysfunctional, but that strategies interfering with inhibitory axes have significant potential to alleviate this dysfunction.


Assuntos
Imunoterapia/métodos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Terapia de Alvo Molecular/métodos , Neoplasias Urogenitais/terapia , Terapia Biológica/métodos , Feminino , Humanos , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Neoplasias Renais/imunologia , Neoplasias Renais/terapia , Masculino , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/terapia , Medição de Risco , Resultado do Tratamento , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/terapia , Neoplasias Urogenitais/imunologia
4.
Cells ; 9(10)2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-33003471

RESUMO

COVID-19, caused by SARS-CoV-2 virus, emerged as a pandemic disease posing a severe threat to global health. To date, sporadic studies have demonstrated that innate immune mechanisms, specifically neutrophilia, NETosis, and neutrophil-associated cytokine responses, are involved in COVID-19 pathogenesis; however, our understanding of the exact nature of this aspect of host-pathogen interaction is limited. Here, we present a detailed dissection of the features and functional profiles of neutrophils, dendritic cells, and monocytes in COVID-19. We portray the crucial role of neutrophils as drivers of hyperinflammation associated with COVID-19 disease via the shift towards their immature forms, enhanced degranulation, cytokine production, and augmented interferon responses. We demonstrate the impaired functionality of COVID-19 dendritic cells and monocytes, particularly their low expression of maturation markers, increased PD-L1 levels, and their inability to upregulate phenotype upon stimulation. In summary, our work highlights important data that prompt further research, as therapeutic targeting of neutrophils and their associated products may hold the potential to reduce the severity of COVID-19.


Assuntos
Infecções por Coronavirus/sangue , Células Dendríticas/imunologia , Monócitos/imunologia , Neutrófilos/imunologia , Pneumonia Viral/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Células Cultivadas , Infecções por Coronavirus/imunologia , Citocinas/genética , Citocinas/metabolismo , Feminino , Humanos , Imunidade Inata , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia
5.
Int J Mol Sci ; 21(19)2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33019591

RESUMO

Tom70 is a versatile adaptor protein of 70 kDa anchored in the outer membrane of mitochondria in metazoa, fungi and amoeba. The tertiary structure was resolved for the Tom70 of yeast, showing 26 α-helices, most of them participating in the formation of 11 tetratricopeptide repeat (TPR) motifs. Tom70 serves as a docking site for cytosolic chaperone proteins and co-chaperones and is thereby involved in the uptake of newly synthesized chaperone-bound proteins in mitochondrial biogenesis. In yeast, Tom70 additionally mediates ER-mitochondria contacts via binding to sterol transporter Lam6/Ltc1. In mammalian cells, TOM70 promotes endoplasmic reticulum (ER) to mitochondria Ca2+ transfer by association with the inositol-1,4,5-triphosphate receptor type 3 (IP3R3). TOM70 is specifically targeted by the Bcl-2-related protein MCL-1 that acts as an anti-apoptotic protein in macrophages infected by intracellular pathogens, but also in many cancer cells. By participating in the recruitment of PINK1 and the E3 ubiquitin ligase Parkin, TOM70 can be implicated in the development of Parkinson's disease. TOM70 acts as receptor of the mitochondrial antiviral-signaling protein (MAVS) and thereby participates in the corresponding system of innate immunity against viral infections. The protein encoded by Orf9b in the genome of SARS-CoV-2 binds to TOM70, probably compromising the synthesis of type I interferons.


Assuntos
Imunidade Inata , Proteínas de Transporte da Membrana Mitocondrial/química , Animais , Betacoronavirus/genética , Sítios de Ligação , Humanos , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Fases de Leitura Aberta , Ligação Proteica , Transporte Proteico
6.
Yakugaku Zasshi ; 140(10): 1259-1268, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32999205

RESUMO

RNA interference (RNAi) is the standard method of suppressing gene expression because of its target specificity, potency, and ability to silence the expression of virtually any gene. Using 21-mer small interfering RNA (siRNA) is the general approach for inducing RNAi, as siRNA can be easily prepared using a DNA/RNA synthesizer. Synthetic siRNA can be chemically modified to increase the potency of RNAi activity and abrogate innate immune stimulation. However, designing chemically modified siRNA requires substantial experimentation. A practical method for understanding the interaction of siRNA and RNAi-related proteins and how modifications affect RNA-protein interactions is therefore needed. Plasmid DNA (pDNA) expressing short hairpin RNA (shRNA) can also be used to induce RNAi. pDNA produces numerous shRNAs that induce RNAi with potent and longterm RNAi activity, even if only one pDNA molecule is delivered to the nucleus. However, this approach has some drawbacks with regard to its therapeutic application, such as a low pDNA transfection efficiency due to its huge molecular size and innate immune responses induced by extra genes, such as CpG motifs. To overcome these issues with RNAi inducers (siRNA and pDNA), our group developed some chemical approaches using chemically modified oligonucleotides. This article focuses on our two original approaches. The first involves the groove modification of siRNA duplexes to understand siRNA-protein interactions using 7-bromo-7-deazaadenosine and 3-bromo-3-deazaadenosine as chemical probes, while the second involves the generation of RNAi medicine using chemically modified DNA, known as an intelligent shRNA expression device (iRed).


Assuntos
Desenvolvimento de Medicamentos/métodos , Interferência de RNA , RNA Interferente Pequeno/síntese química , DNA , Imunidade Inata , Oligonucleotídeos/química , Domínios e Motivos de Interação entre Proteínas , RNA Interferente Pequeno/química , Terapêutica com RNAi , Tubercidina/química
7.
Front Immunol ; 11: 2059, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013871

RESUMO

The novel, highly contagious coronavirus SARS-CoV-2 spreads rapidly throughout the world, leading to a deadly pandemic of a predominantly respiratory illness called COVID-19. Safe and effective anti-SARS-CoV-2 vaccines are urgently needed. However, emerging immunological observations show hallmarks of significant immunopathological characteristics and dysfunctional immune responses in patients with COVID-19. Combined with existing knowledge about immune responses to other closely related and highly pathogenic coronaviruses, this could forebode significant challenges for vaccine development, including the risk of vaccine failure. Animal data from earlier coronavirus vaccine efforts indicate that elderly people, most at risk from severe COVID-19 disease, could be especially at risk from immunopathologic responses to novel coronavirus vaccines. Bacterial "new old friends" such as Bacille Calmette-Guérin (BCG) or Mycobacterium obuense have the ability to elevate basal systemic levels of type 1 cytokines and immune cells, correlating with increased protection against diverse and unrelated infectious agents, called "trained immunity." Here we describe dysfunctional immune responses induced by coronaviruses, representing potentially difficult to overcome obstacles to safe, effective vaccine development for COVID-19, and outline how trained immunity could help protect high risk populations through immunomodulation with BCG and other "new old friends."


Assuntos
Vacina BCG/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunidade Celular , Imunidade Inata , Memória Imunológica/imunologia , Pneumonia Viral/imunologia , Vacinação , Idoso , Animais , Vacinas Anticâncer/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Humanos , Micobactérias não Tuberculosas/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , Risco , Vacinas Virais/efeitos adversos
8.
Oxid Med Cell Longev ; 2020: 6401341, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014275

RESUMO

Human SARS-CoV-2 infection is characterized by a high mortality rate due to some patients developing a large innate immune response associated with a cytokine storm and acute respiratory distress syndrome (ARDS). This is characterized at the molecular level by decreased energy metabolism, altered redox state, oxidative damage, and cell death. Therapies that increase levels of (R)-beta-hydroxybutyrate (R-BHB), such as the ketogenic diet or consuming exogenous ketones, should restore altered energy metabolism and redox state. R-BHB activates anti-inflammatory GPR109A signaling and inhibits the NLRP3 inflammasome and histone deacetylases, while a ketogenic diet has been shown to protect mice from influenza virus infection through a protective γδ T cell response and by increasing electron transport chain gene expression to restore energy metabolism. During a virus-induced cytokine storm, metabolic flexibility is compromised due to increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that damage, downregulate, or inactivate many enzymes of central metabolism including the pyruvate dehydrogenase complex (PDC). This leads to an energy and redox crisis that decreases B and T cell proliferation and results in increased cytokine production and cell death. It is hypothesized that a moderately high-fat diet together with exogenous ketone supplementation at the first signs of respiratory distress will increase mitochondrial metabolism by bypassing the block at PDC. R-BHB-mediated restoration of nucleotide coenzyme ratios and redox state should decrease ROS and RNS to blunt the innate immune response and the associated cytokine storm, allowing the proliferation of cells responsible for adaptive immunity. Limitations of the proposed therapy include the following: it is unknown if human immune and lung cell functions are enhanced by ketosis, the risk of ketoacidosis must be assessed prior to initiating treatment, and permissive dietary fat and carbohydrate levels for exogenous ketones to boost immune function are not yet established. The third limitation could be addressed by studies with influenza-infected mice. A clinical study is warranted where COVID-19 patients consume a permissive diet combined with ketone ester to raise blood ketone levels to 1 to 2 mM with measured outcomes of symptom severity, length of infection, and case fatality rate.


Assuntos
Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/terapia , Dieta Cetogênica/métodos , Cetonas/administração & dosagem , Pneumonia Viral/terapia , Ácido 3-Hidroxibutírico/metabolismo , Imunidade Adaptativa , Animais , Betacoronavirus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/metabolismo , Metabolismo Energético , Humanos , Imunidade Inata , Cetonas/metabolismo , Oxirredução , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo
9.
Acta Med Indones ; 52(3): 306-313, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33020343

RESUMO

Cytokine storm in COVID-19 infection is an excessive immune response to external stimuli where the pathogenesis is complex. The disease progresses rapidly and the mortality is high. Certain evidence shows that the severe deterioration of some patients has been closely related to the strong upregulation of cytokine production in SARS-Co-V2 induced pneumonia with an associated cytokine storm syndrome. Identification of existing approaved therapy with proven safety profile to treat hyperinflammation is critical unmet need in order to reduce COVID-19 associated mortality. To date, no specific therapeutic drugs are available to treat COVID-19 infection. Preliminary studies have shown that immune-modulatory or immune suppressive treatments might be considered as treatment choices for COVID-19, particularly in severe disease. This article review the pathogenesis and treatment strategies of COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.


Assuntos
Betacoronavirus , Infecções por Coronavirus/imunologia , Citocinas/sangue , Gerenciamento Clínico , Imunidade Inata , Pandemias , Pneumonia Viral/imunologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Citocinas/imunologia , Humanos , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia
10.
Front Immunol ; 11: 2059, 2020.
Artigo em Inglês | MEDLINE | ID: covidwho-798018

RESUMO

The novel, highly contagious coronavirus SARS-CoV-2 spreads rapidly throughout the world, leading to a deadly pandemic of a predominantly respiratory illness called COVID-19. Safe and effective anti-SARS-CoV-2 vaccines are urgently needed. However, emerging immunological observations show hallmarks of significant immunopathological characteristics and dysfunctional immune responses in patients with COVID-19. Combined with existing knowledge about immune responses to other closely related and highly pathogenic coronaviruses, this could forebode significant challenges for vaccine development, including the risk of vaccine failure. Animal data from earlier coronavirus vaccine efforts indicate that elderly people, most at risk from severe COVID-19 disease, could be especially at risk from immunopathologic responses to novel coronavirus vaccines. Bacterial "new old friends" such as Bacille Calmette-Guérin (BCG) or Mycobacterium obuense have the ability to elevate basal systemic levels of type 1 cytokines and immune cells, correlating with increased protection against diverse and unrelated infectious agents, called "trained immunity." Here we describe dysfunctional immune responses induced by coronaviruses, representing potentially difficult to overcome obstacles to safe, effective vaccine development for COVID-19, and outline how trained immunity could help protect high risk populations through immunomodulation with BCG and other "new old friends."


Assuntos
Vacina BCG/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunidade Celular , Imunidade Inata , Memória Imunológica/imunologia , Pneumonia Viral/imunologia , Vacinação , Idoso , Animais , Vacinas Anticâncer/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Humanos , Micobactérias não Tuberculosas/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , Risco , Vacinas Virais/efeitos adversos
12.
Acta Med Indones ; 52(3): 306-313, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: covidwho-833768

RESUMO

Cytokine storm in COVID-19 infection is an excessive immune response to external stimuli where the pathogenesis is complex. The disease progresses rapidly and the mortality is high. Certain evidence shows that the severe deterioration of some patients has been closely related to the strong upregulation of cytokine production in SARS-Co-V2 induced pneumonia with an associated cytokine storm syndrome. Identification of existing approaved therapy with proven safety profile to treat hyperinflammation is critical unmet need in order to reduce COVID-19 associated mortality. To date, no specific therapeutic drugs are available to treat COVID-19 infection. Preliminary studies have shown that immune-modulatory or immune suppressive treatments might be considered as treatment choices for COVID-19, particularly in severe disease. This article review the pathogenesis and treatment strategies of COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.


Assuntos
Betacoronavirus , Infecções por Coronavirus/imunologia , Citocinas/sangue , Gerenciamento Clínico , Imunidade Inata , Pandemias , Pneumonia Viral/imunologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Citocinas/imunologia , Humanos , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia
13.
Oxid Med Cell Longev ; 2020: 6401341, 2020.
Artigo em Inglês | MEDLINE | ID: covidwho-813370

RESUMO

Human SARS-CoV-2 infection is characterized by a high mortality rate due to some patients developing a large innate immune response associated with a cytokine storm and acute respiratory distress syndrome (ARDS). This is characterized at the molecular level by decreased energy metabolism, altered redox state, oxidative damage, and cell death. Therapies that increase levels of (R)-beta-hydroxybutyrate (R-BHB), such as the ketogenic diet or consuming exogenous ketones, should restore altered energy metabolism and redox state. R-BHB activates anti-inflammatory GPR109A signaling and inhibits the NLRP3 inflammasome and histone deacetylases, while a ketogenic diet has been shown to protect mice from influenza virus infection through a protective γδ T cell response and by increasing electron transport chain gene expression to restore energy metabolism. During a virus-induced cytokine storm, metabolic flexibility is compromised due to increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that damage, downregulate, or inactivate many enzymes of central metabolism including the pyruvate dehydrogenase complex (PDC). This leads to an energy and redox crisis that decreases B and T cell proliferation and results in increased cytokine production and cell death. It is hypothesized that a moderately high-fat diet together with exogenous ketone supplementation at the first signs of respiratory distress will increase mitochondrial metabolism by bypassing the block at PDC. R-BHB-mediated restoration of nucleotide coenzyme ratios and redox state should decrease ROS and RNS to blunt the innate immune response and the associated cytokine storm, allowing the proliferation of cells responsible for adaptive immunity. Limitations of the proposed therapy include the following: it is unknown if human immune and lung cell functions are enhanced by ketosis, the risk of ketoacidosis must be assessed prior to initiating treatment, and permissive dietary fat and carbohydrate levels for exogenous ketones to boost immune function are not yet established. The third limitation could be addressed by studies with influenza-infected mice. A clinical study is warranted where COVID-19 patients consume a permissive diet combined with ketone ester to raise blood ketone levels to 1 to 2 mM with measured outcomes of symptom severity, length of infection, and case fatality rate.


Assuntos
Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/terapia , Dieta Cetogênica/métodos , Cetonas/administração & dosagem , Pneumonia Viral/terapia , Ácido 3-Hidroxibutírico/metabolismo , Imunidade Adaptativa , Animais , Betacoronavirus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/metabolismo , Metabolismo Energético , Humanos , Imunidade Inata , Cetonas/metabolismo , Oxirredução , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo
14.
Viruses ; 12(10)2020 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-33050511

RESUMO

Herd immunity is the most critical and essential prophylactic intervention that delivers protection against infectious diseases at both the individual and community level. This process of natural vaccination is immensely pertinent to the current context of a pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection around the globe. The conventional idea of herd immunity is based on efficient transmission of pathogens and developing natural immunity within a population. This is entirely encouraging while fighting against any disease in pandemic circumstances. A spatial community is occupied by people having variable resistance capacity against a pathogen. Protection efficacy against once very common diseases like smallpox, poliovirus or measles has been possible only because of either natural vaccination through contagious infections or expanded immunization programs among communities. This has led to achieving herd immunity in some cohorts. The microbiome plays an essential role in developing the body's immune cells for the emerging competent vaccination process, ensuring herd immunity. Frequency of interaction among microbiota, metabolic nutrients and individual immunity preserve the degree of vaccine effectiveness against several pathogens. Microbiome symbiosis regulates pathogen transmissibility and the success of vaccination among different age groups. Imbalance of nutrients perturbs microbiota and abrogates immunity. Thus, a particular population can become vulnerable to the infection. Intestinal dysbiosis leads to environmental enteropathy (EE). As a consequence, the generation of herd immunity can either be delayed or not start in a particular cohort. Moreover, disparities of the protective response of many vaccines in developing countries outside of developed countries are due to inconsistencies of healthy microbiota among the individuals. We suggested that pan-India poliovirus vaccination program, capable of inducing herd immunity among communities for the last 30 years, may also influence the inception of natural course of heterologous immunity against SARS-CoV-2 infection. Nonetheless, this anamnestic recall is somewhat counterintuitive, as antibody generation against original antigens of SARS-CoV-2 will be subdued due to original antigenic sin.


Assuntos
Imunidade Coletiva , Microbiota , Viroses/imunologia , Viroses/microbiologia , Betacoronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/microbiologia , Infecções por Coronavirus/transmissão , Disbiose/imunologia , Humanos , Imunidade Heteróloga , Imunidade Inata , Microbiota/imunologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/microbiologia , Pneumonia Viral/transmissão , Vacinação , Viroses/epidemiologia , Viroses/transmissão
15.
J Endod ; 46(9S): S10-S18, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32950180

RESUMO

INTRODUCTION: The improvement of regenerative endodontic procedures requires an understanding of the key clinical questions combined with a fundamental biological knowledge of how the dental tissues behave during health, disease, and repair. Therefore, partnerships between clinicians and basic scientists are essential to drive the field forward and improve patient outcomes. METHODS: This review aimed to provide a background to dentin-pulp biology and the interaction between infection, inflammation, and regeneration. RESULTS: We have highlighted how the release of neutrophil extracellular traps (NETs) within the pulp are double-edged; while they aim to limit the bacterial infection, they may actually exacerbate cell death and chronic inflammation. Aberrant levels of these structures may occur because of ineffective host immunologic processes, viral infections, or impaired clearance caused by bacterial virulence factors. We also postulate a proinflammatory link in the pulp between NETs and the inflammasome activated by pathogen-associated molecular patterns and damage-associated molecular patterns. Subsequently, we discuss areas potentially fruitful for future clinical exploitation involving NET inhibitors, inflammasome modulators, phototherapies, and novel epigenetic approaches. CONCLUSIONS: Sustained scientist-clinician research partnerships along with an increased understanding of the association between inflammation and regeneration within the dentin-pulp complex will lead to future patient benefit.


Assuntos
Polpa Dentária , Armadilhas Extracelulares , Dentina , Humanos , Imunidade Inata , Regeneração , Endodontia Regenerativa , Engenharia Tecidual
16.
Molecules ; 25(18)2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32906733

RESUMO

On March 11, 2020, the World Health Organization (WHO) officially declared the outbreak caused by the new coronavirus (SARS-CoV-2) a pandemic. The rapid spread of the disease surprised the scientific and medical community. Based on the latest reports, news, and scientific articles published, there is no doubt that the coronavirus has overloaded health systems globally. Practical actions against the recent emergence and rapid expansion of the SARS-CoV-2 require the development and use of tools for discovering new molecular anti-SARS-CoV-2 targets. Thus, this review presents bioinformatics and molecular modeling strategies that aim to assist in the discovery of potential anti-SARS-CoV-2 agents. Besides, we reviewed the relationship between SARS-CoV-2 and innate immunity, since understanding the structures involved in this infection can contribute to the development of new therapeutic targets. Bioinformatics is a technology that assists researchers in coping with diseases by investigating genetic sequencing and seeking structural models of potential molecular targets present in SARS-CoV2. The details provided in this review provide future points of consideration in the field of virology and medical sciences that will contribute to clarifying potential therapeutic targets for anti-SARS-CoV-2 and for understanding the molecular mechanisms responsible for the pathogenesis and virulence of SARS-CoV-2.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Biologia Computacional , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Descoberta de Drogas , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Animais , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/transmissão , Humanos , Imunidade Inata , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/transmissão
17.
Monaldi Arch Chest Dis ; 90(4)2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32945643

RESUMO

Novel coronavirus disease (COVID-19) has affected nearly 7 million individuals and claimed more than 0.4 million lives to date. There are several reports of gender differences related to infection and death due to COVID-19. This raises important questions such as "Whether there are differences based on gender in risk and severity of infection or mortality rate?" and "What are the biological explanation and mechanisms underlying these differences?" Emerging evidences have proposed sex-based immunological, genetic, and hormonal differences to explain this ambiguity. Besides biological differences, women have also faced social inequities and economic hardships due to this pandemic. Several recent studies have shown that independent of age males are at higher risk for severity and mortality in COVID-19 patients. Although susceptibility to SARS-CoV-2 was found to be similar across both genders in several disease cohorts, a disproportionate death ratio in men can be partly explained by the higher burden of pre-existing diseases and occupational exposures among men. At immunological point of view, females can engage a more active immune response, which may protect them and counter infectious diseases as compared to men. This attribute of better immune responses towards pathogens is thought to be due to high estrogen levels in females. Here we review the current knowledge about sex differences in susceptibility, the severity of infection and mortality, host immune responses, and the role of sex hormones in COVID-19 disease.


Assuntos
Imunidade Adaptativa/imunologia , Infecções por Coronavirus/imunologia , Estrogênios/imunologia , Imunidade Inata/imunologia , Pneumonia Viral/imunologia , Testosterona/imunologia , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Mortalidade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Índice de Gravidade de Doença , Caracteres Sexuais , Fatores Sexuais
18.
Nat Commun ; 11(1): 4367, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32868763

RESUMO

Invariant natural killer T (iNKT), mucosal-associated invariant T (MAIT), and γδ T cells are innate T cells that acquire memory phenotype in the thymus and share similar biological characteristics. However, how their effector differentiation is developmentally regulated is still unclear. Here, we identify analogous effector subsets of these three innate T cell types in the thymus that share transcriptional profiles. Using single-cell RNA sequencing, we show that iNKT, MAIT and γδ T cells mature via shared, branched differentiation rather than linear maturation or TCR-mediated instruction. Simultaneous TCR clonotyping analysis reveals that thymic maturation of all three types is accompanied by clonal selection and expansion. Analyses of mice deficient of TBET, GATA3 or RORγt and additional in vivo experiments corroborate the predicted differentiation paths, while human innate T cells from liver samples display similar features. Collectively, our data indicate that innate T cells share effector differentiation processes in the thymus.


Assuntos
Diferenciação Celular , Imunidade Inata , Linfócitos T/metabolismo , Timo/imunologia , Animais , Células Cultivadas , Seleção Clonal Mediada por Antígeno , Humanos , Fígado/citologia , Fígado/imunologia , Ativação Linfocitária , Camundongos , Células T Invariáveis Associadas à Mucosa/metabolismo , Células T Matadoras Naturais/metabolismo , Análise de Sequência de RNA , Análise de Célula Única , Células Th17/metabolismo , Timo/citologia
19.
Artigo em Russo | MEDLINE | ID: mdl-32929928

RESUMO

OBJECTIVE: To determine factors of innate and acquired immunity in adaptation disorders with a predominance of asthenic or anxiety-depressive syndrome. MATERIAL AND METHODS: Twenty-five patients with ICD-10 diagnosis of «Adaptation Disorders¼ (F43.2), including 9 with asthenic syndrome and 16 with anxiety-depressive syndrome, were examined. The control group consisted of 23 healthy individuals. The relative number of lymphocyte phenotypes was determined by flow cytometry; the concentration of IgM, IgG, IgA, aAB to S100b and MBP - by ELISA; CIC level - by the method of selective precipitation with PEG-6000; phagocytic activity of neutrophils by a test system with melamine-formaldehyde latex; activities of leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) by a spectrophotometric method. RESULTS: There were significant changes in the parameters of acquired immunity in the group with asthenic syndrome and those of innate immunity in the group with anxiety-depressive syndrome. An increase in α1-PI activity, in the total number of significant correlations between different immunological parameters, in the involvement of α1-PI in integration of acquired and innate immunity were observed in the anxiety-depressive group compared with the asthenic group. CONCLUSIONS: The peculiarities of stress response in patients with leading anxiety-depressive syndrome are the high activity of α1-PI, which, along with the strengthening of correlation intersystem associations and the involvement of this protein in the integration of acquired and innate immunity, allows us to consider α1-PI as a criterion that improves the accuracy of diagnosis of the nature of the course of adaptation disorders.


Assuntos
Imunidade Adaptativa , Elastase de Leucócito , Astenia , Humanos , Imunidade Inata , alfa 1-Antitripsina
20.
Front Immunol ; 11: 1979, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973803

RESUMO

The new pandemic virus SARS-CoV-2 emerged in China and spread around the world in <3 months, infecting millions of people, and causing countries to shut down public life and businesses. Nearly all nations were unprepared for this pandemic with healthcare systems stretched to their limits due to the lack of an effective vaccine and treatment. Infection with SARS-CoV-2 can lead to Coronavirus disease 2019 (COVID-19). COVID-19 is respiratory disease that can result in a cytokine storm with stark differences in morbidity and mortality between younger and older patient populations. Details regarding mechanisms of viral entry via the respiratory system and immune system correlates of protection or pathogenesis have not been fully elucidated. Here, we provide an overview of the innate immune responses in the lung to the coronaviruses MERS-CoV, SARS-CoV, and SARS-CoV-2. This review provides insight into key innate immune mechanisms that will aid in the development of therapeutics and preventive vaccines for SARS-CoV-2 infection.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunidade Inata , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Pneumonia Viral/imunologia , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Idoso , Idoso de 80 Anos ou mais , Animais , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Feminino , Humanos , Evasão da Resposta Imune , Masculino , Pandemias , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Mucosa Respiratória/imunologia , Síndrome Respiratória Aguda Grave/virologia
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