Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24.721
Filtrar
1.
2.
Front Immunol ; 12: 773352, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745149

RESUMO

Anti-MDA5 dermatomyositis is a rare systemic autoimmune disease, historically described in Japanese patients with clinically amyopathic dermatomyositis and life-threatening rapidly progressive interstitial lung disease. Subsequently, the complete clinical spectrum of the disease was enriched by skin, articular and vascular manifestations. Depending on the predominance of these symptoms, three distinct clinical phenotypes with different prognosis are now defined. To date, the only known molecular component shared by the three entities are specific antibodies targeting MDA5, a cytosolic protein essential for antiviral host immune responses. Several biological tools have emerged to detect these antibodies, with drawbacks and limitations for each of them. However, the identification of this highly specific serological marker of the disease raises the question of its role in the pathogenesis. Although current knowledge on the pathogenic mechanisms that take place in the disease are still in their enfancy, several lines of evidence support a central role of interferon-mediated vasculopathy in the development of skin and lung lesions, as well as a possible pathogenic involvement of anti-MDA5 antibodies. Here, we review the clinical and biological evidences in favor of these hypothesis, and we discuss the contribution of emerging therapies that shed some light on the pathogenesis of the disease.


Assuntos
Autoanticorpos/imunologia , Vasos Sanguíneos/patologia , Dermatomiosite/imunologia , Helicase IFIH1 Induzida por Interferon/imunologia , Doenças Pulmonares Intersticiais/imunologia , Pele/patologia , Animais , Dermatomiosite/terapia , Humanos , Interferons/metabolismo , Doenças Pulmonares Intersticiais/terapia , Fenótipo
3.
Front Cell Infect Microbiol ; 11: 689707, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621686

RESUMO

The induction of antiviral effector proteins as part of a homeostatically controlled innate immune response to infection plays a critical role in limiting the propagation and transmission of respiratory pathogens. However, the prolonged induction of this immune response can lead to lung hyperinflammation, tissue damage, and respiratory failure. We hypothesized that tissues exposed to the constant threat of infection may constitutively express higher levels of antiviral effector proteins to reduce the need to activate potentially harmful innate immune defences. By analysing transcriptomic data derived from a range of human tissues, we identify lung tissue to express constitutively higher levels of antiviral effector genes relative to that of other mucosal and non-mucosal tissues. By using primary cell lines and the airways of rhesus macaques, we show the interferon-stimulated antiviral effector protein TRIM22 (TRIpartite Motif 22) to be constitutively expressed in the lung independently of viral infection or innate immune stimulation. These findings contrast with previous reports that have shown TRIM22 expression in laboratory-adapted cell lines to require interferon stimulation. We demonstrate that constitutive levels of TRIM22 are sufficient to inhibit the onset of human and avian influenza A virus (IAV) infection by restricting the onset of viral transcription independently of interferon-mediated innate immune defences. Thus, we identify TRIM22 to confer a pre-existing (intrinsic) intracellular defence against IAV infection in cells derived from the respiratory tract. Our data highlight the importance of tissue-specific and cell-type dependent patterns of pre-existing immune gene expression in the intracellular restriction of IAV from the outset of infection.


Assuntos
Vírus da Influenza A , Influenza Humana , Animais , Humanos , Imunidade Inata , Interferons , Pulmão , Macaca mulatta , Antígenos de Histocompatibilidade Menor , Proteínas Repressoras , Proteínas com Motivo Tripartido/genética , Replicação Viral
4.
5.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638804

RESUMO

There are three classes of interferons (type 1, 2, and 3) that can contribute to the development and maintenance of various autoimmune diseases, including systemic lupus erythematosus (SLE). Each class of interferons promotes the generation of autoreactive B cells and SLE-associated autoantibodies by distinct signaling mechanisms. SLE patients treated with various type 1 interferon-blocking biologics have diverse outcomes, suggesting that additional environmental and genetic factors may dictate how these cytokines contribute to the development of autoreactive B cells and SLE. Understanding how each class of interferons controls B cell responses in SLE is necessary for developing optimized B cell- and interferon-targeted therapeutics. In this review, we will discuss how each class of interferons differentially promotes the loss of peripheral B cell tolerance and leads to the development of autoreactive B cells, autoantibodies, and SLE.


Assuntos
Linfócitos B/imunologia , Interferons/imunologia , Animais , Autoanticorpos , Humanos , Interferons/metabolismo , Lúpus Eritematoso Sistêmico , Transdução de Sinais
6.
Rheum Dis Clin North Am ; 47(4): 669-690, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635298

RESUMO

Juvenile dermatomyositis (JDM) is a heterogeneous disease with new classification criteria and updates in myositis-specific autoantibody and myositis-associated antibody groups. There are many validated assessment tools for assessing disease activity in JDM. Future studies will optimize these tools and improve feasibility in clinical and research contexts. Genetic and environmental risk factors, mechanisms of muscle pathology, role of interferon, vascular markers, and changes in immune cells provide insights to JDM pathogenesis. Outcomes have improved, but chronic disease, damage, and mortality highlight the need for better outcome predictors and treatments. Increased collaboration of stakeholders may help overcome research barriers and improve JDM treatment.


Assuntos
Dermatomiosite , Miosite , Autoanticorpos , Biomarcadores , Dermatomiosite/diagnóstico , Humanos , Interferons
7.
J Immunol ; 207(11): 2770-2784, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34697227

RESUMO

Circular RNAs (circRNAs) are a subgroup of endogenous noncoding RNA that is covalently closed rings and widely expressed. In recent years, there is accumulating evidence indicating that circRNAs are a class of important regulators, which play an important role in various biological processes. However, the biological functions and regulation mechanism of circRNAs in lower vertebrates are little known. In this study, we discovered a circRNA Samd4a (circSamd4a) that is related to the antiviral immune response of teleost fish. It can act as a key regulator of the host's antiviral response and play a key role in inhibiting Sininiperca chuatsi rhabdovirus replication. Further studies have shown that circSamd4a may act as a competing endogenous RNA, which can enhance the STING-mediated NF-κB/IRF3 signaling pathway by adsorbing miR-29a-3p, thereby enhancing the antiviral immune response. Therefore, circSamd4a plays an active regulatory role in the antiviral immune response of bony fish. Our research results provide a strong foundation for circular RNA to play a regulatory role in the antiviral immune response of teleost fish.


Assuntos
Interferons/imunologia , MicroRNAs/imunologia , RNA Circular/imunologia , Regulação para Cima/imunologia , Animais , Células Cultivadas , Perciformes
8.
J Immunol ; 207(11): 2660-2672, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34706932

RESUMO

Type I IFN is essential for viral clearance but also contributes to the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE), via aberrant nucleic acid-sensing pathways, leading to autoantibody production. Type III IFN (IFN-λ) is now appreciated to have a nonredundant role in viral infection, but few studies have addressed the effects of IFN-λ on immune cells given the more restricted expression of its receptor primarily to the epithelium. In this study, we demonstrate that B cells display a prominent IFN gene expression profile in patients with lupus. Serum levels of IFN-λ are elevated in SLE and positively correlate with B cell subsets associated with autoimmune plasma cell development, including CD11c+T-bet+CD21- B cells. Although B cell subsets express all IFN receptors, IFNLR1 strongly correlates with the CD11c+CD21- B cell expansion, suggesting that IFN-λ may be an unappreciated driver of the SLE IFN signature and B cell abnormalities. We show that IFN-λ potentiates gene transcription in human B cells typically attributed to type I IFN as well as expansion of T-bet-expressing B cells after BCR and TLR7/8 stimulation. Further, IFN-λ promotes TLR7/8-mediated plasmablast differentiation and increased IgM production. CD11c+ B cells demonstrate IFN-λ hyperresponsive signaling compared with other B cell subsets, suggesting that IFN-λ accelerates plasma cell differentiation through this putative extrafollicular pathway. In summary, our data support type III IFN-λ as a cytokine promoting the Ab-secreting cell pool in human viral and autoimmune disease.


Assuntos
Linfócitos B/imunologia , Interferons/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Plasmócitos/imunologia , Adulto , Idoso , Diferenciação Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
Trends Immunol ; 42(11): 1009-1023, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34629295

RESUMO

Interferons (IFNs) are among the first vertebrate immune pathways activated upon viral infection and are crucial for control of viral replication and dissemination, especially at mucosal surfaces as key locations for host exposure to pathogens. Inhibition of viral establishment and spread at and from these mucosal sites is paramount for preventing severe disease, while concomitantly limiting putative detrimental effects of inflammation. Here, we compare the roles of type I, II, and III IFNs in regulating three archetypal viruses - norovirus, herpes simplex virus, and severe acute respiratory virus coronavirus 2 (SARS-CoV-2) - which infect distinct mammalian mucosal tissues. Emerging paradigms include highly specific roles for IFNs in limiting local versus systemic infection, synergistic activities, and a spectrum of protective versus detrimental effects of IFNs during the infection response.


Assuntos
COVID-19 , Viroses , Animais , Humanos , Imunidade Inata , Interferons , Membrana Mucosa , SARS-CoV-2 , Replicação Viral
10.
J Gen Virol ; 102(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34661517

RESUMO

Rabies is a zoonotic disease caused by the rabies virus (RABV). RABV can lead to fatal encephalitis and is still a serious threat in most parts of the world. Interferon regulatory factor 7 (IRF7) is the main transcriptional regulator of type I IFN, and it is crucial for the induction of IFNα/ß and the type I IFN-dependent immune response. In this study, we focused on the role of IRF7 in the pathogenicity and immunogenicity of RABV using an IRF7-/- mouse model. The results showed that the absence of IRF7 made mice more susceptible to RABV, because IRF7 restricted the replication of RABV in the early stage of infection. IRF7 deficiency affected the recruitment of plasmacytoid dendritic cells to the draining lymph nodes (dLNs), reduced the production of type I IFN and expression of IFN-stimulated genes. Furthermore, we found that the ability to produce specific RABV-neutralizing antibody was impaired in IRF7-/- mice. Consistently, IRF7 deficiency affected the recruitment of germinal-centre B cells to dLNs, and the generation of plasma cells and RABV-specific antibody secreting cells. Moreover, the absence of IRF7 downregulated the induction of IFN-γ and reduced type 1 T helper cell (Th1)-dependent antibody production. Collectively, our findings demonstrate that IRF7 promotes humoral immune responses and compromises the pathogenicity of RABV in a mouse model.


Assuntos
Fator Regulador 7 de Interferon/fisiologia , Vírus da Raiva/imunologia , Vírus da Raiva/patogenicidade , Raiva/imunologia , Raiva/virologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Células Produtoras de Anticorpos/imunologia , Linfócitos B/imunologia , Linhagem Celular , Células Dendríticas/imunologia , Modelos Animais de Doenças , Feminino , Imunidade Humoral , Fator Regulador 7 de Interferon/deficiência , Fator Regulador 7 de Interferon/genética , Interferons/análise , Linfonodos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Vacinas Antirrábicas/imunologia , Células Th1/imunologia , Carga Viral
11.
J Gen Virol ; 102(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34661519

RESUMO

Ubiquitin and ubiquitin-like protein modification play important roles in modulating the functions of viral proteins in many viruses. Here we demonstrate that hepatitis B virus (HBV) X protein (HBx) is modified by ISG15, which is a type I IFN-inducible, ubiquitin-like protein; this modification is called ISGylation. Immunoblot analyses revealed that HBx proteins derived from four different HBV genotypes accepted ISGylation in cultured cells. Site-directed mutagenesis revealed that three lysine residues (K91, K95 and K140) on the HBx protein, which are well conserved among all the HBV genotypes, are involved in acceptance of ISGylation. Using expression plasmids encoding three known E3 ligases involved in the ISGylation to different substrates, we found that HERC5 functions as an E3 ligase for HBx-ISGylation. Treatment with type I and type III IFNs resulted in the limited suppression of HBV replication in Hep38.7-Tet cells. When cells were treated with IFN-α, silencing of ISG15 resulted in a marked reduction of HBV replication in Hep38.7-Tet cells, suggesting a role of ISG15 in the resistance to IFN-α. In contrast, the silencing of USP18 (an ISG15 de-conjugating enzyme) increased the HBV replication in Hep38.7-Tet cells. Taken together, these results suggest that the HERC5-mediated ISGylation of HBx protein confers pro-viral functions on HBV replication and participates in the resistance to IFN-α-mediated antiviral activity.


Assuntos
Citocinas/metabolismo , Vírus da Hepatite B/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Transativadores/metabolismo , Ubiquitinas/metabolismo , Proteínas Virais Reguladoras e Acessórias/metabolismo , Replicação Viral , Linhagem Celular , Farmacorresistência Viral , Vírus da Hepatite B/genética , Humanos , Interferon-alfa/farmacologia , Interferon beta/farmacologia , Interferons/farmacologia , Transativadores/química , Ubiquitina Tiolesterase/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Virais Reguladoras e Acessórias/química
12.
PLoS One ; 16(10): e0255309, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34618816

RESUMO

BACKGROUND: Type III interferon, or interferon lambda (IFNλ) is a crucial antiviral cytokine induced by influenza infection. While IFNλ is important for anti-viral host defense, published data demonstrate that IFNλ is pathogenic during influenza/bacterial super-infection. It is known that polymorphisms in specific IFNλ genes affect influenza responses, but the effect of IFNλ subtypes on bacterial super-infection is unknown. METHODS: Using an established model of influenza, Staphylococcus aureus super-infection, we studied IFNλ3-/- and control mice to model a physiologically relevant reduction in IFNλ and to address its role in super-infection. RESULTS: Surprisingly, IFNλ3-/- mice did not have significantly lower total IFNλ than co-housed controls, and displayed no change in viral or bacterial clearance. Importantly, both control and IFNλ3-/- mice displayed a positive correlation between viral burden and total IFNλ in the bronchoalveolar lavage during influenza/bacterial super-infection, suggesting that higher influenza viral burden drives a similar total IFNλ response regardless of IFNλ3 gene integrity. Interestingly, total IFNλ levels positively correlated with bacterial burden, while viral burden and bronchoalveolar lavage cellularity did not. CONCLUSIONS: These data suggest IFNλ2 can compensate for IFNλ3 to mount an effective antiviral and defense, revealing a functional redundancy in these highly similar IFNλ subtypes. Further, the IFNλ response to influenza, as opposed to changes in cellular inflammation or viral load, significantly correlates with susceptibility to bacterial super-infection. Moreover, the IFNλ response is regulated and involves redundant subtypes, suggesting it is of high importance to pulmonary pathogen defense.


Assuntos
Interferons/análise , Interferons/imunologia , Interleucinas/imunologia , Infecções por Orthomyxoviridae/imunologia , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/imunologia , Animais , Linhagem Celular , Coinfecção/imunologia , Coinfecção/microbiologia , Cães , Feminino , Interferons/genética , Interleucinas/genética , Células Madin Darby de Rim Canino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infecções por Orthomyxoviridae/patologia , Polimorfismo Genético/genética , Infecções Estafilocócicas/prevenção & controle , Superinfecção/imunologia , Superinfecção/microbiologia , Carga Viral/imunologia
13.
J Gen Virol ; 102(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34698626

RESUMO

Human noroviruses (HuNoVs) are increasingly becoming the main cause of transmissible gastroenteritis worldwide, with hundreds of thousands of deaths recorded annually. Yet, decades after their discovery, there is still no effective treatment or vaccine. Efforts aimed at developing vaccines or treatment will benefit from a greater understanding of norovirus-host interactions, including the host response to infection. In this review, we provide a concise overview of the evidence establishing the significance of type I and type III interferon (IFN) responses in the restriction of noroviruses. We also critically examine our current understanding of the molecular mechanisms of IFN induction in norovirus-infected cells, and outline the diverse strategies deployed by noroviruses to supress and/or avoid host IFN responses. It is our hope that this review will facilitate further discussion and increase interest in this area.


Assuntos
Infecções por Caliciviridae/imunologia , Infecções por Caliciviridae/virologia , Interferons/fisiologia , Norovirus/imunologia , Norovirus/patogenicidade , Animais , Linhagem Celular , Humanos , Evasão da Resposta Imune , Imunidade Inata , Interferons/biossíntese , Proteínas Virais/metabolismo , Replicação Viral
14.
Front Immunol ; 12: 720205, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504497

RESUMO

Patients with the monogenic immune dysregulatory syndrome autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), which is caused by loss-of-function mutations in the autoimmune regulator (AIRE) gene, uniformly carry neutralizing autoantibodies directed against type-I interferons (IFNs) and many develop autoimmune pneumonitis, both of which place them at high risk for life-threatening COVID-19 pneumonia. Bamlanivimab and etesevimab are monoclonal antibodies (mAbs) that target the SARS-CoV-2 spike protein and block entry of SARS-CoV-2 in host cells. The use of bamlanivimab and etesevimab early during infection was associated with reduced COVID-19-associated hospitalization and death in patients at high risk for progressing to severe disease, which led the US Food and Drug Administration to issue an emergency use authorization for their administration in non-hypoxemic, non-hospitalized high-risk patients. However, the safety and efficacy of these mAbs has not been evaluated in APECED patients. We enrolled two siblings with APECED on an IRB-approved protocol (NCT01386437) and admitted them prophylactically at the NIH Clinical Center for evaluation of mild-to-moderate COVID-19. We assessed the safety and clinical effects of early treatment with bamlanivimab and etesevimab. The administration of bamlanivimab and etesevimab was well tolerated and was associated with amelioration of COVID-19 symptoms and prevention of invasive ventilatory support, admission to the intensive care, and death in both patients without affecting the production of antibodies to the nucleocapsid protein of SARS-CoV-2. If given early in the course of COVID-19 infection, bamlanivimab and etesevimab may be beneficial in APECED and other high-risk patients with neutralizing autoantibodies directed against type-I IFNs.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , COVID-19/tratamento farmacológico , Poliendocrinopatias Autoimunes/tratamento farmacológico , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , COVID-19/complicações , COVID-19/genética , COVID-19/imunologia , Feminino , Humanos , Interferons/genética , Interferons/imunologia , Masculino , Mutação , Poliendocrinopatias Autoimunes/complicações , Poliendocrinopatias Autoimunes/genética , Poliendocrinopatias Autoimunes/imunologia , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Fatores de Transcrição/genética , Fatores de Transcrição/imunologia
15.
Int J Mol Sci ; 22(18)2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34576307

RESUMO

In the era of personalized medicine, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as asthma phenotypes including obesity-associated asthma, are urgently needed. Peripheral blood was drawn from 10 obese, non-atopic asthmatic adults with a high body mass index (BMI; 36.67 ± 6.90); 10 non-obese, non-atopic asthmatic adults with normal BMI (23.88 ± 2.73); and 10 healthy controls with normal BMI (23.62 ± 3.74). All asthmatic patients were considered to represent a low type-2 asthma phenotype according to selective clinical parameters. RNA sequencing (RNA-Seq) was conducted on peripheral blood CD4+ T cells. Thousands of differentially expressed genes were identified in both asthma groups compared with heathy controls. The expression of interferon (IFN)-stimulated genes associated with IFN-related signaling pathways was specifically affected in obese asthmatics, while the gap junction and G protein-coupled receptor (GPCR) ligand binding pathways were enriched in both asthma groups. Furthermore, obesity gene markers were also upregulated in CD4+ T cells from obese asthmatics compared with the two other groups. Additionally, the enriched genes of the three abovementioned pathways showed a unique correlation pattern with various laboratory and clinical parameters. The specific activation of IFN-related signaling and viral infection pathways might provide a novel view of the molecular mechanisms associated with the development of the low type-2 obesity-associated asthma phenotype, which is a step ahead in the development of new stratified therapeutic approaches.


Assuntos
Asma/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Interferons/metabolismo , Obesidade/metabolismo , Transdução de Sinais , Adulto , Asma/complicações , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Receptores Acoplados a Proteínas G/metabolismo
16.
Cell Rep ; 37(1): 109773, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34587479

RESUMO

SARS-CoV-2 infection in children is less severe than it is in adults. We perform a longitudinal analysis of the early innate responses in children and adults with mild infection within household clusters. Children display fewer symptoms than adults do, despite similar initial viral load, and mount a robust anti-viral immune signature typical of the SARS-CoV-2 infection and characterized by early interferon gene responses; increases in cytokines, such as CXCL10 and GM-CSF; and changes in blood cell numbers. When compared with adults, the antiviral response resolves faster (within a week of symptoms), monocytes and dendritic cells are more transiently activated, and genes associated with B cell activation appear earlier in children. Nonetheless, these differences do not have major effects on the quality of SARS-CoV-2-specific antibody responses. Our findings reveal that better early control of inflammation as observed in children may be key for rapidly controlling infection and limiting the disease course.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/genética , COVID-19/imunologia , Citocinas/metabolismo , Imunidade Inata , SARS-CoV-2/imunologia , Transcriptoma , Imunidade Adaptativa , Adolescente , Adulto , Linfócitos B/metabolismo , COVID-19/virologia , Quimiocina CXCL10/metabolismo , Criança , Pré-Escolar , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Lactente , Inflamação/virologia , Interferons/metabolismo , Estudos Longitudinais , Pessoa de Meia-Idade , Monócitos/metabolismo , Análise de Sequência de RNA , Carga Viral , Adulto Jovem
17.
J Laryngol Otol ; 135(11): 958-963, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34470689

RESUMO

BACKGROUND: Recurrent respiratory papillomatosis is a potentially life-threatening condition characterised by the growth of exophytic lesions within the larynx and trachea. The principal aim of management is maintenance of an adequate airway by surgical debulking. Several adjuvant therapies have been used to varying effect to reduce the burden of this disease and increase the interval between debulking procedures. The most severe cases present in children aged under three years, who are therefore most likely to need adjuvant therapies. The current evidence base on adjuvant treatments relating to children who present aged under three years has been reviewed. METHODS: A literature review of articles in Cochrane, PubMed and Embase databases was carried out. Given the rarity of the condition in this age group, all the literature relates to case reports and case series. RESULTS AND CONCLUSION: The following adjuvant therapies have been used in children who presented under three years of age: quadrivalent human papilloma virus vaccine, intralesional cidofovir, pegylated interferon, alpha-interferon, cimetidine and cetuximab.


Assuntos
Antivirais/uso terapêutico , Quimioterapia Adjuvante/métodos , Infecções por Papillomavirus/terapia , Infecções Respiratórias/terapia , Cetuximab/uso terapêutico , Cidofovir/uso terapêutico , Cimetidina/uso terapêutico , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Lactente , Interferon-alfa/uso terapêutico , Interferons/uso terapêutico , Masculino , Infecções por Papillomavirus/virologia , Infecções Respiratórias/virologia , Resultado do Tratamento
18.
J Infect Dis ; 224(5): 777-782, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34467988

RESUMO

We analyzed plasma levels of interferons (IFNs) and cytokines, and expression of IFN-stimulated genes in peripheral blood mononuclear cells in patients with coronavirus disease 2019 of varying disease severity. Patients hospitalized with mild disease exhibited transient type I IFN responses, while intensive care unit patients had prolonged type I IFN responses. Type II IFN responses were compromised in intensive care unit patients. Type III IFN responses were induced in the early phase of infection, even in convalescent patients. These results highlight the importance of early type I and III IFN responses in controlling coronavirus disease 2019 progression.


Assuntos
COVID-19/imunologia , Interferon Tipo I/imunologia , Interferon gama/imunologia , Interferons/imunologia , COVID-19/sangue , Quimiocinas/sangue , Citocinas/sangue , Humanos , Interferon Tipo I/sangue , Interferon Tipo I/genética , Interferon gama/sangue , Interferon gama/genética , Interferons/sangue , Leucócitos Mononucleares/imunologia , SARS-CoV-2/isolamento & purificação
19.
Liver Int ; 41(11): 2547-2559, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34520597

RESUMO

In their never-ending quest towards persistence within their host, hepatitis viruses have developed numerous ways to counteract the liver innate immunity. This review highlights the different and common mechanisms employed by these viruses to (i) establish in the liver (passive entry or active evasion from immune recognition) and (ii) actively inhibit the innate immune response (ie modulation of pattern recognition receptor expression and/or signalling pathways, modulation of interferon response and modulation of immune cells count or phenotype).


Assuntos
Imunidade Inata , Vírus , Interferons , Fígado , Receptores de Reconhecimento de Padrão
20.
Cell ; 184(19): 4953-4968.e16, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34492226

RESUMO

Severe coronavirus disease 2019 (COVID-19) is characterized by overproduction of immune mediators, but the role of interferons (IFNs) of the type I (IFN-I) or type III (IFN-III) families remains debated. We scrutinized the production of IFNs along the respiratory tract of COVID-19 patients and found that high levels of IFN-III, and to a lesser extent IFN-I, characterize the upper airways of patients with high viral burden but reduced disease risk or severity. Production of specific IFN-III, but not IFN-I, members denotes patients with a mild pathology and efficiently drives the transcription of genes that protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In contrast, compared to subjects with other infectious or noninfectious lung pathologies, IFNs are overrepresented in the lower airways of patients with severe COVID-19 that exhibit gene pathways associated with increased apoptosis and decreased proliferation. Our data demonstrate a dynamic production of IFNs in SARS-CoV-2-infected patients and show IFNs play opposing roles at distinct anatomical sites.


Assuntos
COVID-19/patologia , Interferons/metabolismo , Sistema Respiratório/virologia , Índice de Gravidade de Doença , Fatores Etários , Envelhecimento/patologia , COVID-19/genética , COVID-19/imunologia , Células Epiteliais/patologia , Células Epiteliais/virologia , Regulação da Expressão Gênica , Humanos , Interferons/genética , Leucócitos/patologia , Leucócitos/virologia , Pulmão/patologia , Pulmão/virologia , Síndrome do Desconforto Respiratório/patologia , Síndrome do Desconforto Respiratório/virologia , Carga Viral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...