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1.
Anticancer Res ; 40(10): 5355-5359, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988854

RESUMO

BACKGROUND/AIM: Recent studies indicate that chimeric antigen receptor (CAR)-T-cells seem to be superior to CAR modified NK-92 cells. One, at least partial, explanation to this discrepancy has been addressed herein, by having NK-92 cells as target cells in cytotoxicity reactions using peripheral blood mononuclear cells. MATERIALS AND METHODS: A time-resolved fluorometric assay (TDA-labeled NK-92 or K562 as target cells) was used for measuring the cytotoxic activity of blood mononuclear cells (PBMC). RESULTS: The cytotoxic capacity of the NK-92 cells was initially demonstrated by their ability to efficiently kill K562 cells. Interestingly, having PBMC as effector cells rendered the very same NK-92 cells sensitive to NK-cell mediated cytolysis. A 1:100 target:effector ratio gave 34.1% lysis compared to 72.2% lysis for K562 cells. Incubating PBMC for longer times (24 up to 48 h) potentiated their NK-activity against NK-92 cells even more, reaching a level close to that obtained with K562 cells. CONCLUSION: This study pinpoints a severe problem that has to be considered in future immune-based cancer therapies with NK-92 as well as CAR-transduced NK-92 cells.


Assuntos
Imunoterapia Adotiva , Células Matadoras Naturais/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Neoplasias/terapia , Citotoxicidade Imunológica/efeitos dos fármacos , Humanos , Imunidade Celular/efeitos dos fármacos , Imunidade Celular/imunologia , Interleucina-2/genética , Interleucina-2/imunologia , Células K562 , Neoplasias/imunologia , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/imunologia
2.
Lancet Oncol ; 21(9): e419-e430, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32888471

RESUMO

Notable advances have been achieved in the treatment of cancer since the advent of immunotherapy, and immune checkpoint inhibitors have shown clinical benefit across a wide variety of tumour types. Nevertheless, most patients still progress on these treatments, highlighting the importance of unravelling the underlying mechanisms of primary resistance to immunotherapy. A well described biomarker of non-responsiveness to immune checkpoint inhibitors is the absence or low presence of lymphocytes in the tumour microenvironment, so-called cold tumours. There are five mechanisms of action that have the potential to turn cold tumours into so-called hot and inflamed tumours, hence increasing the tumour's responsiveness to immunotherapy-increasing local inflammation, neutralising immunosuppression at the tumour site, modifying the tumour vasculature, targeting the tumour cells themselves, or increasing the frequency of tumour-specific T cells. In this Review, we discuss preclinical data that serves as the basis for ongoing immunotherapy clinical trials for the treatment of non-immunoreactive tumours, as well as reviewing clinical and translational data where available. We explain how improving our understanding of the underlying mechanisms of primary resistance to immunotherapy will help elucidate an increasingly granular view of the tumour microenvironment cellular composition, functional status, and cellular localisation, with the goal of further therapy refinement.


Assuntos
Resistencia a Medicamentos Antineoplásicos/imunologia , Imunoterapia/efeitos adversos , Inflamação/terapia , Neoplasias/terapia , Microambiente Tumoral/efeitos dos fármacos , Antineoplásicos Imunológicos/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Quinase 1 do Ponto de Checagem/antagonistas & inibidores , Quinase 1 do Ponto de Checagem/imunologia , Ensaios Clínicos como Assunto , Humanos , Imunidade Celular/imunologia , Inflamação/imunologia , Inflamação/patologia , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Neoplasias/imunologia , Neoplasias/patologia , Microambiente Tumoral/imunologia
3.
Hum Immunol ; 81(10-11): 588-595, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32888767

RESUMO

Coronavirus Disease 2019 (COVID-19) is a dangerous global threat that has no clinically approved treatment yet. Bioinformatics represent an outstanding approach to reveal key immunogenic regions in viral proteins. Here, five severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structural proteins (NSPs) (NSP7, NSP8, NSP9, NSP12, and NSP13) were screened to identify potential human leukocyte antigen (HLA) binding peptides. These peptides showed robust viral antigenicity, immunogenicity, and a marked interaction with HLA alleles. Interestingly, several peptides showed affinity by HLA class I (HLA-I) alleles that commonly activates to natural killer (NK) cells. Notably, HLA biding peptides are conserved among SARS-CoV-2, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). Interestingly, HLA-I and HLA class II (HLA-II) binding peptides induced humoral and cell-mediated responses after in silico vaccination. These results may open further in vitro and in vivo investigations to develop novel therapeutic strategies against coronaviral infections.


Assuntos
Betacoronavirus/imunologia , Sequência Conservada/imunologia , Infecções por Coronavirus/imunologia , Antígenos HLA/imunologia , Pneumonia Viral/imunologia , Proteínas não Estruturais Virais/imunologia , Sequência de Aminoácidos , Betacoronavirus/genética , Infecções por Coronavirus/sangue , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Antígenos HLA/metabolismo , Humanos , Imunidade Celular/imunologia , Imunidade Humoral/imunologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Simulação de Acoplamento Molecular , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Vírus da SARS/genética , Vírus da SARS/imunologia , Vacinas de Subunidades/imunologia , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Vacinas Virais/imunologia
4.
Sheng Wu Gong Cheng Xue Bao ; 36(7): 1440-1449, 2020 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-32748602

RESUMO

Hepatitis B virus core protein can self-assemble into icosahedral symmetrical viral-like particles (VLPs) in vitro, and display exogenous sequences repeatedly and densely on the surface. VLPs also have strong immunogenicity and biological activity. When the nanoparticles enter the body, they quickly induce specific humoral and cellular immune responses to exogenous antigens. In this study, we designed an HBc-VLPs that can be coupled with antigens at specific sites, and developed a set of efficient methods to prepare HBc-VLPs. Through site-specific mutation technology, the 80th amino acid of peptide was changed from Ala to Cys, a specific cross-linking site was inserted into the main immunodominant region of HBc-VLPs, and the prokaryotic expression vector pET28a(+)-hbc was constructed. After expression and purification, high purity HBc(A80C) monomer protein was assembled into HBc-VLPs nanoparticles in Phosphate Buffer. The results of particle size analysis show that the average particle size of nanoparticles was 29.8 nm. Transmission electron microscopy (TEM) showed that HBc-VLPs formed spherical particles with a particle size of about 30 nm, and its morphology was similar to that of natural HBV particles. The influenza virus antigen M2e peptide as model antigen was connected to Cys residue of HBc-VLPs by Sulfo-SMCC, an amino sulfhydryl bifunctional cross-linking agent, and M2e-HBc-VLPs model vaccine was prepared. The integrity of HBc-VLPs structure and the correct cross-linking of M2e were verified by cell fluorescence tracing. Animal immune experiments showed that the vaccine can effectively stimulate the production of antigen-specific IgG antibody in mice, which verified the effectiveness of the vaccine carrier HBc-VLPs. This study lays a foundation for the research of HBc-VLPs as vaccine vector, and help to promote the development of HBc-VLPs vaccine and the application of HBc-VLPs in other fields.


Assuntos
Antígenos do Núcleo do Vírus da Hepatite B , Imunidade Celular , Vacinas de Partículas Semelhantes a Vírus , Animais , Antígenos do Núcleo do Vírus da Hepatite B/genética , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Imunidade Celular/imunologia , Imunoglobulina G/sangue , Camundongos , Camundongos Endogâmicos BALB C , Vacinas de Partículas Semelhantes a Vírus/genética , Vacinas de Partículas Semelhantes a Vírus/imunologia
7.
Mult Scler ; 26(10): 1261-1264, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32762494

RESUMO

Approximately 200,000 multiple sclerosis (MS) patients worldwide receive B-cell-depleting immunotherapy with rituximab (anti-CD20), which eliminates the ability to generate an antibody response to new infections. As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies might help viral clearance, these patients could be at risk of severe complications if infected. Here, we report on an MS patient who had received rituximab for ~3 years. The patient was examined 5 days before the onset of coronavirus disease 2019 (COVID-19) symptoms and was admitted to the hospital 2 days after. She recovered 14 days after symptom onset despite having a 0% B lymphocyte count and not developing SARS-CoV-2 immunoglobulin G (IgG) antibodies.


Assuntos
Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Infecções por Coronavirus/imunologia , Imunidade Celular/imunologia , Células Matadoras Naturais/imunologia , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Pneumonia Viral/imunologia , Rituximab/uso terapêutico , Betacoronavirus , Relação CD4-CD8 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Progressão da Doença , Feminino , Humanos , Contagem de Linfócitos , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/complicações , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia
8.
Medicine (Baltimore) ; 99(27): e21010, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629720

RESUMO

The net level of immunosuppression in kidney transplant recipients is difficult to assess. QuantiFERON Monitor (QFM) is an in vitro diagnostic test that detects interferon-γ (IFN-γ) release in peripheral blood. The aim of our study was to compare QFM testing results in stable kidney transplant recipients and kidney transplant recipients with infection, in a single-centre cohort.We enrolled 71 kidney transplant recipients from our transplantation centre. They were divided into 2 groups according to clinical presentation (Stable kidney transplant recipients or Infection).There were no significant differences in interferon-γ release between the 2 groups (Stable kidney transplant recipients 140.59 ±â€Š215.28 IU/ml, Infection group 78.37 ±â€Š197.03 IU/ml, P = .24). A further analysis revealed that kidney transplant recipients presenting with bacterial infection had significantly lower IFN-γ release when compared to stable kidney transplant recipients (26.52 ±â€Š42.46 IU/ml vs 140.59 ±â€Š215.28 IU/ml, P = .04).Kidney transplant recipients presenting with bacterial infection had lower IFN-γ release when compared to stable kidney transplant recipients. The QFM test may be useful as a tool to help guide immunosuppression dosing in kidney transplant recipients, but further studies are required to confirm its diagnostic value.


Assuntos
Imunossupressão/efeitos adversos , Testes de Liberação de Interferon-gama/métodos , Interferon gama/sangue , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Imunidade Celular/imunologia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Transplantados/estatística & dados numéricos
9.
ACS Chem Neurosci ; 11(15): 2149-2151, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32662981

RESUMO

Acanthamoeba and macrophages exhibit significant parallels in biochemical, physiological, cellular, and functional aspects. Given the ability of Acanthamoeba to contribute to the evolutionary gain of pathogenicity of a variety of microbial pathogens, here we propose the use of Acanthamoeba as a paradigm to study SARS-CoV-2 pathogenicity, infectivity, and evasion of cellular immune defenses.


Assuntos
Acanthamoeba/imunologia , Betacoronavirus , Infecções por Coronavirus/imunologia , Imunidade Celular/imunologia , Fagócitos/imunologia , Pneumonia Viral/imunologia , Animais , Infecções por Coronavirus/patologia , Infecções por Coronavirus/transmissão , Humanos , Pandemias , Fagócitos/patologia , Fagocitose/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/transmissão
10.
Parasitol Res ; 119(9): 2885-2895, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32715344

RESUMO

Chicken coccidiosis is a protozoan parasitic disease that leads to considerable economic losses in the poultry industry. In this study, we used invasive Lactobacillus plantarum (L.P) expressing the FnBPA protein as a novel bacterial carrier for DNA delivery into epithelial cells to develop a live oral DNA vaccine. A fusion DNA vaccine co-expressing EtMIC2 and chicken IL-18 (chIL-18) was constructed and then delivered to the host by invasive L.P. Its efficacy against Eimeria tenella challenge was evaluated in chickens by examining the relative weight gain rate; caecal lesion score; OPG; anti-coccidial index (ACI); levels of EtMIC2 antibody, FnBPA, IL-4, IL-18, IFN-γ and SIgA; and proliferation ability and percentages of CD4+ and CD8+ splenocytes. The experimental results showed that chickens immunized with invasive L.P carrying the eukaryotic expression vector pValac-EtMIC2 (pValac-EtMIC2/pSIP409-FnBPA) had markedly improved immune protection against challenge compared with that of chickens immunized with non-invasive L.P (pValac-EtMIC2/pSIP409). However, invasive L.P co-expressing EtMIC2 with the chIL-18 vector exhibited the highest protection efficiency against E. tenella. These results indicate that invasive Lactobacillus-expressing FnBPA improved humoural and cellular immunity and enhanced resistance to E. tenella. The DNA vaccine delivered by invasive Lactobacillus provides a new concept and method for the prevention of E. tenella.


Assuntos
Antígeno 12E7/metabolismo , Coccidiose/veterinária , Eimeria tenella/imunologia , Interleucina-18/metabolismo , Lactobacillus plantarum/metabolismo , Vacinas Protozoárias/imunologia , Vacinas de DNA/imunologia , Animais , Ceco/parasitologia , Galinhas/parasitologia , Coccidiose/parasitologia , Eimeria tenella/genética , Imunidade Celular/imunologia , Imunoglobulina A Secretora/genética , Lactobacillus plantarum/genética , Doenças das Aves Domésticas/parasitologia , Doenças das Aves Domésticas/prevenção & controle , Vacinação/veterinária , Ganho de Peso
11.
Nat Med ; 26(9): 1428-1434, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32661393

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has dramatically expedited global vaccine development efforts1-3, most targeting the viral 'spike' glycoprotein (S). S localizes on the virion surface and mediates recognition of cellular receptor angiotensin-converting enzyme 2 (ACE2)4-6. Eliciting neutralizing antibodies that block S-ACE2 interaction7-9, or indirectly prevent membrane fusion10, constitute an attractive modality for vaccine-elicited protection11. However, although prototypic S-based vaccines show promise in animal models12-14, the immunogenic properties of S in humans are poorly resolved. In this study, we characterized humoral and circulating follicular helper T cell (cTFH) immunity against spike in recovered patients with coronavirus disease 2019 (COVID-19). We found that S-specific antibodies, memory B cells and cTFH are consistently elicited after SARS-CoV-2 infection, demarking robust humoral immunity and positively associated with plasma neutralizing activity. Comparatively low frequencies of B cells or cTFH specific for the receptor binding domain of S were elicited. Notably, the phenotype of S-specific cTFH differentiated subjects with potent neutralizing responses, providing a potential biomarker of potency for S-based vaccines entering the clinic. Overall, although patients who recovered from COVID-19 displayed multiple hallmarks of effective immune recognition of S, the wide spectrum of neutralizing activity observed suggests that vaccines might require strategies to selectively target the most potent neutralizing epitopes.


Assuntos
Anticorpos Neutralizantes/farmacologia , Infecções por Coronavirus/imunologia , Peptidil Dipeptidase A/genética , Pneumonia Viral/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/farmacologia , Antígenos Virais/imunologia , Chlorocebus aethiops , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Epitopos/imunologia , Humanos , Imunidade Celular/imunologia , Pandemias , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Linfócitos T Auxiliares-Indutores/imunologia , Células Vero/imunologia
12.
Nat Rev Immunol ; 20(8): 499-506, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32493982

RESUMO

We are just beginning to understand the diversity of the peripheral T cell compartment, which arises from the specialization of different T cell subsets and the plasticity of individual naive T cells to adopt different fates. Although the progeny of a single T cell can differentiate into many phenotypes following infection, individual T cells are biased towards particular phenotypes. These biases are typically ascribed to random factors that occur during and after antigenic stimulation. However, the T cell compartment does not remain static with age, and shifting immune challenges during ontogeny give rise to T cells with distinct functional properties. Here, we argue that the developmental history of naive T cells creates a 'hidden layer' of diversity that persists into adulthood. Insight into this diversity can provide a new perspective on immunity and immunotherapy across the lifespan.


Assuntos
Imunidade Celular/imunologia , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/imunologia , Animais , Diferenciação Celular/imunologia , Humanos , Memória Imunológica/imunologia , Camundongos , Receptores de Antígenos de Linfócitos T/imunologia
13.
Jpn J Radiol ; 38(10): 942-952, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32533391

RESUMO

PURPOSE: To explore the dynamic changes and correlation between CT imaging manifestations and cellular immunity of COVID-19. MATERIALS AND METHODS: This retrospective review analyzed 23 patients with COVID-19, including 13 males and 10 females aged 27-70 years, with an average age of 48 years. Patients were divided into two groups: group A with 11 critical-severe patients, and group B with 12 common-mild patients. Clinical, laboratory, and radiological data were collected and analyzed. RESULTS: LYM, LYM (%), CD3+, CD4+, and CD8+ decreased, while NEU (%), CRP, and CT scores increased in all patients, WBC in group A increased. In group A, on day 10-12 after disease onset, CT scores and CRP reached the highest point, and day 13-15 LYM, LYM (%) reached the lowest but NEU (%) and WBC reached the highest, CD3+, CD4+ and CD8+ were at the lowest on day 10-15. In group B, on day 7-9, CT scores, NEU (%) and CRP reached the peak, but LYM, LYM (%), CD3+, CD4+ and CD8+ reached the lowest. In all patients, CT scores had a significantly negative correlation with CD3+, CD4+, CD8+, LYM (%), and LYM (p = 0.001, r = - 0.797; p = 0.008, r = - 0.698; p = 0.002, r = - 0.775; p < 0.001, r = - 0.785; p = 0.021, r = - 0.571, respectively), and a significantly positive correlation with WBC and NEU (%) (p < 0.001, r = 0.785; p = 0.003, r = 0.691, respectively). CONCLUSION: Dynamic changes of CT manifestations and cellular immunity of patients with COVID-19 were regular and correlation was high between these two parameters.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunidade Celular/imunologia , Pulmão/diagnóstico por imagem , Pulmão/imunologia , Pneumonia Viral/imunologia , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Infecções por Coronavirus/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico por imagem , Curva ROC , Estudos Retrospectivos
14.
Glia ; 68(11): 2345-2360, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32449994

RESUMO

The present study examines functional contributions of microglia in host defense, demyelination, and remyelination following infection of susceptible mice with a neurotropic coronavirus. Treatment with PLX5622, an inhibitor of colony stimulating factor 1 receptor (CSF1R) that efficiently depletes microglia, prior to infection of the central nervous system (CNS) with the neurotropic JHM strain of mouse hepatitis virus (JHMV) resulted in increased mortality compared with control mice that correlated with impaired control of viral replication. Single cell RNA sequencing (scRNASeq) of CD45+ cells isolated from the CNS revealed that PLX5622 treatment resulted in muted CD4+ T cell activation profile that was associated with decreased expression of transcripts encoding MHC class II and CD86 in macrophages but not dendritic cells. Evaluation of spinal cord demyelination revealed a marked increase in white matter damage in PLX5622-treated mice that corresponded with elevated expression of transcripts encoding disease-associated proteins Osteopontin (Spp1), Apolipoprotein E (Apoe), and Triggering receptor expressed on myeloid cells 2 (Trem2) that were enriched within macrophages. In addition, PLX5622 treatment dampened expression of Cystatin F (Cst7), Insulin growth factor 1 (Igf1), and lipoprotein lipase (Lpl) within macrophage populations which have been implicated in promoting repair of damaged nerve tissue and this was associated with impaired remyelination. Collectively, these findings argue that microglia tailor the CNS microenvironment to enhance control of coronavirus replication as well as dampen the severity of demyelination and influence repair.


Assuntos
Encéfalo/imunologia , Infecções por Coronavirus/imunologia , Interações Hospedeiro-Patógeno/imunologia , Microglia/imunologia , Vírus da Hepatite Murina/imunologia , Compostos Orgânicos/toxicidade , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/virologia , Infecções por Coronavirus/induzido quimicamente , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Imunidade Celular/efeitos dos fármacos , Imunidade Celular/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/virologia
15.
J Neuroimmunol ; 344: 577246, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32371201

RESUMO

We examined the relationship between CSF immune cells and neurocognition and neuronal damage in HIV+ individuals before and after initiating antiretroviral therapy. Multivariate analysis at baseline indicated that greater CD4+ T cell abundance was associated with better cognition (p = .017), while higher CSF HIV RNA was associated with increased neuronal damage (p = .014). Following 24 weeks of antiretroviral therapy, CD8+ T cells, HLA-DR expressing CD4+ and CD8+ T cells, B cells, NK cells, and non-classical monocyte percentage decreased in CSF. Female gender was negatively associated with cognitive performance over time, as was higher percentage of HLA-DR expressing CD8+ T cells at baseline.


Assuntos
Terapia Antirretroviral de Alta Atividade/métodos , Cognição/fisiologia , Infecções por HIV/líquido cefalorraquidiano , Infecções por HIV/imunologia , Imunidade Celular/imunologia , Carga Viral/imunologia , Adulto , Cognição/efeitos dos fármacos , Feminino , Seguimentos , Infecções por HIV/tratamento farmacológico , Humanos , Imunidade Celular/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga Viral/efeitos dos fármacos
16.
J Neuroimmunol ; 344: 577263, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32416557

RESUMO

The Th17 profile immune response is influenced by the presence of cytokines such as IL-1, IL-6, TGF-ß, IL-17, and IL-23. We sought to characterize the Th17 profile in CNS samples from human rabies cases transmitted by dogs and examine its possible influence on disease pathogenesis. We observed a high expression of TGF-ß, followed by IL-23, IL-17 and IL-6, and a low expression of IL-1ß and IFN-γ. Those results suggest the participation of Th17 in rabies virus neuroinfection transmitted by dogs. IL-23 probably plays a role in maintaining the Th17 profile, but it can also interfere with the establishment of the Th1 profile and viral clearance.


Assuntos
Encéfalo/imunologia , Citocinas/imunologia , Imunidade Celular/imunologia , Raiva/imunologia , Raiva/transmissão , Células Th17/imunologia , Adolescente , Adulto , Animais , Encéfalo/metabolismo , Citocinas/metabolismo , Cães , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Raiva/metabolismo , Células Th17/metabolismo , Adulto Jovem
17.
Nat Med ; 26(6): 932-940, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32393800

RESUMO

Recent efforts toward an HIV vaccine focus on inducing broadly neutralizing antibodies, but eliciting both neutralizing antibodies (nAbs) and cellular responses may be superior. Here, we immunized macaques with an HIV envelope trimer, either alone to induce nAbs, or together with a heterologous viral vector regimen to elicit nAbs and cellular immunity, including CD8+ tissue-resident memory T cells. After ten vaginal challenges with autologous virus, protection was observed in both vaccine groups at 53.3% and 66.7%, respectively. A nAb titer >300 was generally associated with protection but in the heterologous viral vector + nAb group, titers <300 were sufficient. In this group, protection was durable as the animals resisted six more challenges 5 months later. Antigen stimulation of T cells in ex vivo vaginal tissue cultures triggered antiviral responses in myeloid and CD4+ T cells. We propose that cellular immune responses reduce the threshold of nAbs required to confer superior and durable protection.


Assuntos
Anticorpos Neutralizantes/efeitos dos fármacos , Anticorpos Antivirais/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Produtos do Gene gag/genética , Imunidade Celular/efeitos dos fármacos , Vacinas contra a SAIDS/farmacologia , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vírus da Imunodeficiência Símia/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Produtos do Gene gag/imunologia , Vetores Genéticos , Imunidade Celular/imunologia , Imunidade Heteróloga , Imunogenicidade da Vacina , Memória Imunológica/imunologia , Macaca mulatta , Membrana Mucosa , Vagina
18.
Diabetes Metab Syndr ; 14(4): 489-496, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32388326

RESUMO

BACKGROUND AND AIMS: COVID-19 is a public world crisis, however, it is a self-limited infection. In COVID-19, the strength of immune and respiratory systems is a critical element. Thus, this review was conducted to demonstrate the short and long term effects of increasing the aerobic capacity on increasing the function and strength of immune and respiratory systems, particularly those essential for overcoming COVID-19 infections and associated disorders. METHODS: This review was carried out by searching in Web of Science, Scopus, EBSCO, Medline databases. The search was conducted over clinical trials and literature and systematic reviews on the effects of increasing the aerobic capacity on the function and strength of specific immune and respiratory elements essential for overcoming COVID-19 infections. RESULTS: This review found that increasing the aerobic capacity could produce short-term safe improvements in the function of immune and respiratory systems, particularly those specific for COVID-19 infections. This could be mainly produced through three mechanisms. Firstly, it could improve immunity by increasing the level and function of immune cells and immunoglobulins, regulating CRP levels, and decreasing anxiety and depression. Secondly, it could improve respiratory system functions by acting as an antibiotic, antioxidant, and antimycotic, restoring normal lung tissue elasticity and strength. Lastly, it could act as a protective barrier to decrease COVID-19 risk factors, which helps to decrease the incidence and progression of COVID-19. CONCLUSION: This review summarizes that increasing the aerobic capacity is recommended because it has potential of improving immune and respiratory functions which would help counter COVID-19.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Exercício Físico , Imunidade Celular/imunologia , Controle de Infecções/métodos , Oxigênio/metabolismo , Pandemias/prevenção & controle , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Sistema Respiratório/imunologia , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Humanos , Pneumonia Viral/transmissão , Pneumonia Viral/virologia
19.
Future Oncol ; 16(20): 1475-1485, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32468851

RESUMO

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a worldwide sanitary emergency. The viral biology is only partially known, with some aspects in common with other coronaviruses, and the damage observed in the most severe cases is due to intense inflammation. Immunotherapy restores immunological activity against cancer cells and it has become a standard treatment for several cancers. We carried out an examination of available data on the effects exerted by both SARS-CoV-2 and the most widespread immunotherapy treatments on the immune system in order to hypothesize mechanisms underlying potential and mutual interaction. We provided an analysis of laboratory, clinical and therapeutic data related with severe acute respiratory syndrome coronavirus. We finally focused on implications of immunotherapy treatments in clinical practice.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/terapia , Imunoterapia/métodos , Neoplasias/terapia , Pneumonia Viral/terapia , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/patologia , Humanos , Imunidade Celular/imunologia , Imunidade Humoral/imunologia , Interleucina-6/antagonistas & inibidores , Neoplasias/patologia , Pandemias , Pneumonia Viral/patologia
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