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2.
Sci Immunol ; 5(51)2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943497

RESUMO

COVID-19 pathogenesis is associated with an exaggerated immune response. However, the specific cellular mediators and inflammatory components driving diverse clinical disease outcomes remain poorly understood. We undertook longitudinal immune profiling on both whole blood and peripheral blood mononuclear cells (PBMCs) of hospitalized patients during the peak of the COVID-19 pandemic in the UK. Here, we report key immune signatures present shortly after hospital admission that were associated with the severity of COVID-19. Immune signatures were related to shifts in neutrophil to T cell ratio, elevated serum IL-6, MCP-1 and IP-10, and most strikingly, modulation of CD14+ monocyte phenotype and function. Modified features of CD14+ monocytes included poor induction of the prostaglandin-producing enzyme, COX-2, as well as enhanced expression of the cell cycle marker Ki-67. Longitudinal analysis revealed reversion of some immune features back to the healthy median level in patients with a good eventual outcome. These findings identify previously unappreciated alterations in the innate immune compartment of COVID-19 patients and lend support to the idea that therapeutic strategies targeting release of myeloid cells from bone marrow should be considered in this disease. Moreover, they demonstrate that features of an exaggerated immune response are present early after hospital admission suggesting immune-modulating therapies would be most beneficial at early timepoints.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunidade Inata , Monócitos/imunologia , Pneumonia Viral/imunologia , Adulto , Idoso , Biomarcadores/sangue , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Ciclo-Oxigenase 2/imunologia , Ciclo-Oxigenase 2/metabolismo , Progressão da Doença , Feminino , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Mediadores da Inflamação/sangue , Mediadores da Inflamação/imunologia , Antígeno Ki-67/imunologia , Antígeno Ki-67/metabolismo , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Estudos Prospectivos , Índice de Gravidade de Doença , Reino Unido/epidemiologia
3.
Nat Commun ; 11(1): 4475, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32901029

RESUMO

Tissue resident memory CD8+ T cells (Trm) are poised for immediate reactivation at sites of pathogen entry and provide optimal protection of mucosal surfaces. The intestinal tract represents a portal of entry for many infectious agents; however, to date specific strategies to enhance Trm responses at this site are lacking. Here, we present TMDI (Transient Microbiota Depletion-boosted Immunization), an approach that leverages antibiotic treatment to temporarily restrain microbiota-mediated colonization resistance, and favor intestinal expansion to high densities of an orally-delivered Listeria monocytogenes strain carrying an antigen of choice. By augmenting the local chemotactic gradient as well as the antigenic load, this procedure generates a highly expanded pool of functional, antigen-specific intestinal Trm, ultimately enhancing protection against infectious re-challenge in mice. We propose that TMDI is a useful model to dissect the requirements for optimal Trm responses in the intestine, and also a potential platform to devise novel mucosal vaccination approaches.


Assuntos
Microbioma Gastrointestinal/imunologia , Imunidade nas Mucosas , Administração Oral , Animais , Antígenos/administração & dosagem , Linfócitos T CD8-Positivos/imunologia , Quimiotaxia/imunologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/imunologia , Imunidade nas Mucosas/efeitos dos fármacos , Memória Imunológica , Listeria monocytogenes/crescimento & desenvolvimento , Listeria monocytogenes/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ovalbumina/administração & dosagem , Estreptomicina/administração & dosagem
4.
Comput Math Methods Med ; 2020: 1352982, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908574

RESUMO

The current emergence of coronavirus (SARS-CoV-2) puts the world in threat. The structural research on the receptor recognition by SARS-CoV-2 has identified the key interactions between SARS-CoV-2 spike protein and its host (epithelial cell) receptor, also known as angiotensin-converting enzyme 2 (ACE2). It controls both the cross-species and human-to-human transmissions of SARS-CoV-2. In view of this, we propose and analyze a mathematical model for investigating the effect of CTL responses over the viral mutation to control the viral infection when a postinfection immunostimulant drug (pidotimod) is administered at regular intervals. Dynamics of the system with and without impulses have been analyzed using the basic reproduction number. This study shows that the proper dosing interval and drug dose both are important to eradicate the viral infection.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Modelos Biológicos , Pneumonia Viral/tratamento farmacológico , Ácido Pirrolidonocarboxílico/análogos & derivados , Tiazolidinas/administração & dosagem , Número Básico de Reprodução , Betacoronavirus/genética , Betacoronavirus/imunologia , Simulação por Computador , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Relação Dose-Resposta a Droga , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Conceitos Matemáticos , Mutação , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Ácido Pirrolidonocarboxílico/administração & dosagem , Receptores Virais/fisiologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T Citotóxicos/imunologia
5.
PLoS One ; 15(9): e0238425, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32960889

RESUMO

OBJECTIVE: To evaluate the effects of Bifidobacterium animalis subsp. lactis HN019 (HN019) on clinical periodontal parameters (plaque accumulation and gingival bleeding), on immunocompetence of gingival tissues [expression of beta-defensin (BD)-3, toll-like receptor 4 (TLR4), cluster of differentiation(CD)-57 and CD-4], and on immunological properties of saliva (IgA levels) in non-surgical periodontal therapy in generalized chronic periodontitis (GCP) patients. Adhesion to buccal epithelial cells (BEC) and the antimicrobial properties of HN019 were also investigated. MATERIALS AND METHODS: Thirty patients were recruited and monitored clinically at baseline (before scaling and root planing-SRP) and after 30 and 90 days. Patients were randomly assigned to Test (SRP+Probiotic, n = 15) or Control (SRP+Placebo, n = 15) group. Probiotic lozenges were used for 30 days. Gingival tissues and saliva were immunologically analyzed. The adhesion of HN019 with or without Porphyromonas gingivalis in BEC and its antimicrobial properties were investigated in in vitro assays. Data were statistically analyzed (p<0.05). RESULTS: Test group presented lower plaque index (30 days) and lower marginal gingival bleeding (90 days) when compared with Control group. Higher BD-3, TLR4 and CD-4 expressions were observed in gingival tissues in Test group than in Control group. HN019 reduced the adhesion of P. gingivalis to BEC and showed antimicrobial potential against periodontopathogens. CONCLUSION: Immunological and antimicrobial properties of B. lactis HN019 make it a potential probiotic to be used in non-surgical periodontal therapy of patients with GCP. CLINICAL RELEVANCE: B. lactis HN019 may be a potential probiotic to improve the effects of non-surgical periodontal therapy. Name of the registry and registration number (ClinicalTrials.gov): "Effects of probiotic therapy in the treatment of periodontitis"-NCT03408548.


Assuntos
Bifidobacterium animalis/imunologia , Periodontite Crônica/terapia , Probióticos/uso terapêutico , Adulto , Aderência Bacteriana/imunologia , Infecções por Bacteroidaceae/imunologia , Infecções por Bacteroidaceae/microbiologia , Infecções por Bacteroidaceae/terapia , Periodontite Crônica/imunologia , Periodontite Crônica/microbiologia , Método Duplo-Cego , Feminino , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Imunoglobulina A Secretora/metabolismo , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/imunologia , Mucosa Bucal/microbiologia , Porphyromonas gingivalis/patogenicidade , Saliva/imunologia
6.
Math Biosci Eng ; 17(4): 2853-2861, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-32987502

RESUMO

In this work, we use a within-host viral dynamic model to describe the SARS-CoV-2 kinetics in the host. Chest radiograph score data are used to estimate the parameters of that model. Our result shows that the basic reproductive number of SARS-CoV-2 in host growth is around 3.79. Using the same method we also estimate the basic reproductive number of MERS virus is 8.16 which is higher than SARS-CoV-2. The PRCC method is used to analyze the sensitivities of model parameters. Moreover, the drug effects on virus growth and immunity effect of patients are also implemented to analyze the model.


Assuntos
Betacoronavirus , Infecções por Coronavirus/virologia , Interações entre Hospedeiro e Microrganismos , Pandemias , Pneumonia Viral/virologia , Número Básico de Reprodução/estatística & dados numéricos , Simulação por Computador , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Cinética , Conceitos Matemáticos , Coronavírus da Síndrome Respiratória do Oriente Médio , Modelos Biológicos , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão
7.
Math Biosci ; 328: 108438, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32771304

RESUMO

Coronavirus disease 2019 (COVID-19), an infectious disease caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading and causing the global coronavirus pandemic. The viral dynamics of SARS-CoV-2 infection have not been quantitatively investigated. In this paper, we use mathematical models to study the pathogenic features of SARS-CoV-2 infection by examining the interaction between the virus, cells and immune responses. Models are fit to the data of SARS-CoV-2 infection in patients and non-human primates. Data fitting and numerical simulation show that viral dynamics of SARS-CoV-2 infection have a few distinct stages. In the initial stage, viral load increases rapidly and reaches the peak, followed by a plateau phase possibly generated by lymphocytes as a secondary target of infection. In the last stage, viral load declines due to the emergence of adaptive immune responses. When the initiation of seroconversion is late or slow, the model predicts viral rebound and prolonged viral persistence, consistent with the observation in non-human primates. Using the model we also evaluate the effect of several potential therapeutic interventions for SARS-CoV-2 infection. Model simulation shows that anti-inflammatory treatments or antiviral drugs combined with interferon are effective in reducing the duration of the viral plateau phase and diminishing the time to recovery. These results provide insights for understanding the infection dynamics and might help develop treatment strategies against COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/virologia , Modelos Biológicos , Pneumonia Viral/virologia , Imunidade Adaptativa , Animais , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/genética , Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Macaca mulatta , Conceitos Matemáticos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , RNA Viral/análise , RNA Viral/genética , Carga Viral
8.
Cell Host Microbe ; 28(3): 465-474.e4, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32798445

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of human infections, and an effective vaccine is critical to mitigate coronavirus-induced disease 2019 (COVID-19). Previously, we developed a replication-competent vesicular stomatitis virus (VSV) expressing a modified form of the SARS-CoV-2 spike gene in place of the native glycoprotein gene (VSV-eGFP-SARS-CoV-2). Here, we show that vaccination with VSV-eGFP-SARS-CoV-2 generates neutralizing immune responses and protects mice from SARS-CoV-2. Immunization of mice with VSV-eGFP-SARS-CoV-2 elicits high antibody titers that neutralize SARS-CoV-2 and target the receptor binding domain that engages human angiotensin-converting enzyme-2 (ACE2). Upon challenge with a human isolate of SARS-CoV-2, mice that expressed human ACE2 and were immunized with VSV-eGFP-SARS-CoV-2 show profoundly reduced viral infection and inflammation in the lung, indicating protection against pneumonia. Passive transfer of sera from VSV-eGFP-SARS-CoV-2-immunized animals also protects naive mice from SARS-CoV-2 challenge. These data support development of VSV-SARS-CoV-2 as an attenuated, replication-competent vaccine against SARS-CoV-2.


Assuntos
Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vírus da Estomatite Vesicular Indiana/genética , Vacinas Virais/genética , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Chlorocebus aethiops , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Vetores Genéticos , Proteínas de Fluorescência Verde/genética , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Peptidil Dipeptidase A/genética , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Receptores Virais/genética , Pesquisa Médica Translacional , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/farmacologia , Células Vero , Vírus da Estomatite Vesicular Indiana/imunologia , Vacinas Virais/imunologia , Vacinas Virais/farmacologia
9.
Cell Host Microbe ; 28(3): 475-485.e5, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32735849

RESUMO

Antibody-based interventions against SARS-CoV-2 could limit morbidity, mortality, and possibly transmission. An anticipated correlate of such countermeasures is the level of neutralizing antibodies against the SARS-CoV-2 spike protein, which engages with host ACE2 receptor for entry. Using an infectious molecular clone of vesicular stomatitis virus (VSV) expressing eGFP as a marker of infection, we replaced the glycoprotein gene (G) with the spike protein of SARS-CoV-2 (VSV-eGFP-SARS-CoV-2) and developed a high-throughput-imaging-based neutralization assay at biosafety level 2. We also developed a focus-reduction neutralization test with a clinical isolate of SARS-CoV-2 at biosafety level 3. Comparing the neutralizing activities of various antibodies and ACE2-Fc soluble decoy protein in both assays revealed a high degree of concordance. These assays will help define correlates of protection for antibody-based countermeasures and vaccines against SARS-CoV-2. Additionally, replication-competent VSV-eGFP-SARS-CoV-2 provides a tool for testing inhibitors of SARS-CoV-2 mediated entry under reduced biosafety containment.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/terapia , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/terapia , Animais , Betacoronavirus/genética , Betacoronavirus/fisiologia , Chlorocebus aethiops , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Proteínas de Fluorescência Verde/genética , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Imunização Passiva , Testes de Neutralização , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Células Vero , Vírus da Estomatite Vesicular Indiana/genética , Vírus da Estomatite Vesicular Indiana/imunologia , Internalização do Vírus , Replicação Viral
10.
Artigo em Inglês | MEDLINE | ID: mdl-32798444

RESUMO

The explosive spread of SARS-CoV-2 suggests that a vaccine will be required to end this global pandemic. Progress in SARS-CoV-2 vaccine development to date has been faster than for any other pathogen in history. Multiple SARS-CoV-2 vaccine candidates have been evaluated in preclinical models and are currently in clinical trials. In this Perspective, we discuss three topics that are critical for SARS-CoV-2 vaccine development: antigen selection and engineering, preclinical challenge studies in non-human primate models, and immune correlates of protection.


Assuntos
Betacoronavirus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Vacinas Virais/isolamento & purificação , Animais , Antígenos Virais/química , Antígenos Virais/genética , Betacoronavirus/genética , Betacoronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Imunidade Celular , Imunidade Humoral , Imunidade Inata , Modelos Animais , Pneumonia Viral/epidemiologia , Primatas , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia
11.
Mediators Inflamm ; 2020: 7527953, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32724296

RESUMO

COVID-19 is a pandemic disease caused by the new coronavirus SARS-CoV-2 that mostly affects the respiratory system. The consequent inflammation is not able to clear viruses. The persistent excessive inflammatory response can build up a clinical picture that is very difficult to manage and potentially fatal. Modulating the immune response plays a key role in fighting the disease. One of the main defence systems is the activation of neutrophils that release neutrophil extracellular traps (NETs) under the stimulus of autophagy. Various molecules can induce NETosis and autophagy; some potent activators are damage-associated molecular patterns (DAMPs) and, in particular, the high-mobility group box 1 (HMGB1). This molecule is released by damaged lung cells and can induce a robust innate immunity response. The increase in HMGB1 and NETosis could lead to sustained inflammation due to SARS-CoV-2 infection. Therefore, blocking these molecules might be useful in COVID-19 treatment and should be further studied in the context of targeted therapy.


Assuntos
Alarminas/imunologia , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Armadilhas Extracelulares/imunologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Alarminas/antagonistas & inibidores , Autofagia/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/patologia , Armadilhas Extracelulares/efeitos dos fármacos , Proteína HMGB1/antagonistas & inibidores , Proteína HMGB1/imunologia , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Interleucina-6/antagonistas & inibidores , Interleucina-6/imunologia , Pulmão/imunologia , Pulmão/patologia , Pandemias , Pneumonia Viral/patologia
12.
Theranostics ; 10(16): 7034-7052, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32641977

RESUMO

This review provides an update for the international research community on the cell modeling tools that could accelerate the understanding of SARS-CoV-2 infection mechanisms and could thus speed up the development of vaccines and therapeutic agents against COVID-19. Many bioengineering groups are actively developing frontier tools that are capable of providing realistic three-dimensional (3D) models for biological research, including cell culture scaffolds, microfluidic chambers for the culture of tissue equivalents and organoids, and implantable windows for intravital imaging. Here, we review the most innovative study models based on these bioengineering tools in the context of virology and vaccinology. To make it easier for scientists working on SARS-CoV-2 to identify and apply specific tools, we discuss how they could accelerate the discovery and preclinical development of antiviral drugs and vaccines, compared to conventional models.


Assuntos
Antivirais/isolamento & purificação , Antivirais/farmacologia , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/prevenção & controle , Vacinas Virais/isolamento & purificação , Vacinas Virais/farmacologia , Betacoronavirus/química , Betacoronavirus/genética , Betacoronavirus/imunologia , Bioengenharia/métodos , Bioengenharia/tendências , Reatores Biológicos , Técnicas de Cultura de Células , Simulação por Computador , Infecções por Coronavirus/imunologia , Descoberta de Drogas/métodos , Descoberta de Drogas/tendências , Avaliação de Medicamentos/métodos , Avaliação de Medicamentos/tendências , Farmacorresistência Viral , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Modelos Biológicos , Organoides/citologia , Organoides/virologia , Pneumonia Viral/imunologia , Nanomedicina Teranóstica
13.
Med Hypotheses ; 143: 110080, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32683221

RESUMO

Coronaviruses including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, also known as 2019-nCoV especially in China) replicate and divide in host cells. During this they are partly hidden from the innate immune responses although inflammatory consequences of viral replication still occur. We propose that anti-inflammatory antiviral prostaglandins may not only restrict viral replication but also prevent inflammatory responses in the lungs and other vital organs that are known to be part of the immuno-pathogenesis of coronavirus disease-19 (COVID-19). The combination of anti-inflammatory antiviral prostaglandins with interferons may lead to the clearance of viruses inside growth-restricted infected cells. However, further experimental studies and clinical trials should be conducted to evaluate the safety and efficacy of these possible therapies.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Prostaglandina D2/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/etiologia , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Modelos Biológicos , Pandemias , Pneumonia Viral/etiologia , Pesquisa Médica Translacional
14.
PLoS One ; 15(7): e0235476, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32609751

RESUMO

To explore the molecular mechanism of the effect of Bacillus cereus PAS38 on the immunity of broilers, sixty 7-day-old broilers were divided into two groups with three replicates. The control group was fed with basal diet, and the treatment group was fed with basal diet containing Bacillus cereus PAS38 1×106 CFU/g. Thymus and bursa of fabricius were taken from two groups of broilers at the age of 42 days, total RNA was extracted, differential gene library was constructed by SSH technology, and immune-related differential genes were screened. Then, we used siRNA to interfere with the expression of some differential genes in the original generation lymphocytes of broiler blood to detect the change of cytokines mRNA expression level. A total of 42 immune-related differentially expressed genes were screened, including 22 up-regulated genes and 20 down-regulated genes. When 7 differentially up-regulated genes associated with enhanced immune function were interfered with in lymphocytes, some immune-promoting cytokines were down-regulated. These results showed that Bacillus cereus PAS38 might up-regulate the expression of JCHAIN, PRDX1, CD3E, CDK6 and other genes in immune organs of broilers, thereby affecting the development of immune organs, the expression of various cytokines and the transduction of immune signals, improving the immune capacity of broilers.


Assuntos
Bacillus cereus/imunologia , Bolsa de Fabricius , Galinhas , Interações entre Hospedeiro e Microrganismos/imunologia , Probióticos/farmacologia , Timo , Animais , Bolsa de Fabricius/efeitos dos fármacos , Bolsa de Fabricius/imunologia , Galinhas/imunologia , Galinhas/microbiologia , Citocinas/genética , Citocinas/imunologia , Técnicas de Hibridização Subtrativa/métodos , Timo/efeitos dos fármacos , Timo/imunologia
16.
Arch Virol ; 165(10): 2279-2289, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32719955

RESUMO

In the early stage of virus infection, the pattern recognition receptor (PRR) signaling pathway of the host cell is activated to induce interferon production, activating interferon-stimulated genes (ISGs) that encode antiviral proteins that exert antiviral effects. Viperin is one of the innate antiviral proteins that exert broad-spectrum antiviral effects by various mechanisms. Porcine epidemic diarrhea virus (PEDV) is a coronavirus that causes huge losses to the pig industry. Research on early antiviral responses in the gastrointestinal tract is essential for developing strategies to prevent the spread of PEDV. In this study, we investigated the mechanisms of viperin in PEDV-infected IPEJ-C2 cells. Increased expression of interferon and viperin and decreased replication of PEDV with a clear reduction in the viral load were observed in PEDV-infected IPEC-J2 cells. Amino acids 1-50 of porcine viperin contain an endoplasmic reticulum signal sequence that allows viperin to be anchored to the endoplasmic reticulum and are necessary for its function in inhibiting PEDV proliferation. The interaction of the viperin S-adenosylmethionine domain with the N protein of PEDV was confirmed via confocal laser scanning microscopy and co-immunoprecipitation. This interaction might interfere with viral replication or assembly to reduce virus proliferation. Our results highlight a potential mechanism whereby viperin is able to inhibit PEDV replication and play an antiviral role in innate immunity.


Assuntos
Antivirais/metabolismo , Interações entre Hospedeiro e Microrganismos/fisiologia , Proteínas do Nucleocapsídeo/fisiologia , Vírus da Diarreia Epidêmica Suína/fisiologia , Animais , Linhagem Celular , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/imunologia , Imunidade Inata , Interferons/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Proteínas do Nucleocapsídeo/antagonistas & inibidores , Proteínas do Nucleocapsídeo/química , Vírus da Diarreia Epidêmica Suína/imunologia , Vírus da Diarreia Epidêmica Suína/patogenicidade , Domínios e Motivos de Interação entre Proteínas , Proteínas/química , Proteínas/genética , Proteínas/fisiologia , Interferência de RNA , Suínos , Replicação Viral
17.
Med Hypotheses ; 143: 110066, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32629204

RESUMO

The COVID-19 pandemic has not spared any continent. The disease has affected more than 7,500,000 individuals globally and killed approximately 450,000 individuals. The disease is caused by a very small virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is an enveloped single-stranded RNA virus with a spike-like structure on its envelope that can interact with the angiotensin-converting enzyme 2 (ACE2) receptor after cleavage. ACE2 receptors are present in the human lungs and other organs. SARS-CoV-2 is a new virus that belongs to the subgenus Sarbecovirus; viruses in this subgenus have spread widely in the previous years and caused outbreaks of severe acute respiratory syndromes.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Modelos Imunológicos , Pneumonia Viral/imunologia , Ageusia/etiologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Expectorantes/uso terapêutico , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/virologia , Muco/metabolismo , Transtornos do Olfato/etiologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/virologia , Fatores de Transcrição SOXB1/metabolismo
18.
Med Hypotheses ; 143: 110073, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32645660

RESUMO

COVID-19 (coronavirus disease 2019) pandemic due to infection with SARS-CoV-2 has led to the death of thousands of adults worldwide. It is now clear that the hyper-inflammatory response triggered by SARS-CoV-2 plays a major role in disease severity and lethality of the infection. Macrophages are innate immune cells that sense and respond to infections by producing a plethora of inflammatory molecules and by interacting with other inflammatory cells. Therefore, macrophages may be diriment on eliminating pathogens and promoting organ repair. However, macrophages can be a major player of the so called cytokine storm and may be damaging to the tissues. It is believed that macrophage activation syndrome is induced by SARS-CoV to be lethal. Surprisingly and fortunately few children die from COVID-19. For instance, in Italy, out of more than 30.000 deaths for COVID-19, three are children. Therefore, we must wonder why? Are macrophages different in children compared to adults? In my opinion they are different. It has been demonstrated that macrophages populate the lung in three "developmental waves", and it has been suggested that similar waves may be observed in other important organs, such as the heart and kidney. It is most likely that macrophages heterogeneity is involved in determining the severity. There are no doubts that macrophages are important in determining life or death in these patients. Comparing macrophages of children with those of adults with different degrees of disease severity is, therefore, mandatory.


Assuntos
Betacoronavirus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Macrófagos/imunologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Adulto , Fatores Etários , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Criança , Infecções por Coronavirus/complicações , Síndrome da Liberação de Citocina/etiologia , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Pulmão/imunologia , Ativação de Macrófagos , Síndrome de Ativação Macrofágica/etiologia , Macrófagos/classificação , Modelos Biológicos , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/complicações
19.
Eur J Pharmacol ; 882: 173329, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32615182

RESUMO

Coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a newly discovered highly pathogenic virus that was declared pandemic in March 2020 by the World Health Organization. The virus affects the respiratory system, produces an inflammatory storm that causes lung damage and respiratory dysfunction. It infects humans of all ages. The Covid-19 takes a more severe course in individuals with chronic metabolic diseases such as obesity, diabetes mellitus, and hypertension. This category of persons exhibits weak immune activity and decreased levels of endogenous antioxidants. Melatonin is a multifunctional signaling hormone synthesized and secreted primarily by the pineal gland. It is a potent antioxidant with immunomodulatory action and has remarkable anti-inflammatory effects under a variety of circumstances. Regarding Covid-19 and metabolic syndrome, adequate information about the relationship between these two comorbidities is required for better management of these patients. Since Covid-19 infection and complications involve severe inflammation and oxidative stress in people with obesity and diabetes, we anticipated the inclusion of melatonin, as powerful antioxidant, within proposed treatment protocols. In this context, melatonin is a potential and promising agent to help overcome Covid-19 infection and boost the immune system in healthy persons and obese and diabetic patients. This review summarizes some evidence from recently published reports on the utility of melatonin as a potential adjuvant in Covid-19-infected individuals with diabetes and obesity.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Diabetes Mellitus/imunologia , Melatonina/farmacologia , Obesidade/imunologia , Pneumonia Viral/tratamento farmacológico , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , Betacoronavirus/patogenicidade , Ensaios Clínicos como Assunto , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Diabetes Mellitus/epidemiologia , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Sistema Imunitário/efeitos dos fármacos , Pulmão , Melatonina/uso terapêutico , Obesidade/epidemiologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Fatores de Risco , Resultado do Tratamento
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