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2.
EBioMedicine ; 45: 303-313, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262714

RESUMO

BACKGROUND: The complement system is a central component of the innate immune system. Constitutive biosynthesis of complement proteins is essential for homeostasis. Dysregulation as a consequence of genetic or environmental cues can lead to inflammatory syndromes or increased susceptibility to infection. However, very little is known about steady state levels in children or its kinetics during infection. METHODS: With a newly developed multiplex mass spectrometry-based method we analyzed the levels of 32 complement proteins in healthy individuals and in a group of pediatric patients infected with bacterial or viral pathogens. FINDINGS: In plasma from young infants we found reduced levels of C4BP, ficolin-3, factor B, classical pathway components C1QA, C1QB, C1QC, C1R, and terminal pathway components C5, C8, C9, as compared to healthy adults; whereas the majority of complement regulating (inhibitory) proteins reach adult levels at very young age. Both viral and bacterial infections in children generally lead to a slight overall increase in complement levels, with some exceptions. The kinetics of complement levels during invasive bacterial infections only showed minor changes, except for a significant increase and decrease of CRP and clusterin, respectively. INTERPRETATION: The combination of lower levels of activating and higher levels of regulating complement proteins, would potentially raise the threshold of activation, which might lead to suppressed complement activation in the first phase of life. There is hardly any measurable complement consumption during bacterial or viral infection. Altogether, expression of the complement proteins appears surprisingly stable, which suggests that the system is continuously replenished. FUND: European Union's Horizon 2020, project PERFORM, grant agreement No. 668303.


Assuntos
Doenças Transmissíveis/imunologia , Ativação do Complemento/imunologia , Proteínas do Sistema Complemento/química , Inflamação/imunologia , Adolescente , Adulto , Proteína C-Reativa/genética , Proteína C-Reativa/imunologia , Criança , Pré-Escolar , Clusterina/genética , Clusterina/imunologia , Doenças Transmissíveis/genética , Ativação do Complemento/genética , Proteínas do Sistema Complemento/classificação , Proteínas do Sistema Complemento/isolamento & purificação , Feminino , Homeostase , Humanos , Lactente , Recém-Nascido , Inflamação/genética , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Adulto Jovem
3.
J Immunol Res ; 2019: 6279360, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31192265

RESUMO

The avian immune system improves with the development of the lymphoid organs. The chickens' spleen serves as the largest peripheral lymphoid organ, but little immunological research has been conducted on that spleen during postembryonic development. We investigated the blood-spleen barrier (BSB) by developing morphological architecture, resistance to the corpuscular antigen, immunocyte distribution, gene expression levels of TLR2/4 and cytokines in the spleens of hatched chickens of differing ages. Results demonstrated that the resistance of exogenous carbon particles of the BSB improved with the morphological and structural development of the chicken spleens. The cuboidal endothelial cells which lined the sheathed capillaries were gradually visible, and the discontinuous basement membrane was thickened during postembryonic development. There was an increased number of T and B cells and antigen-presenting cells in the chicken spleen between hatching and adulthood. The mRNA expression levels of TLR2/4, IL-2, IFN-γ, and TNF-α were higher two weeks after hatching, but these decreased and remain stable between 21 and 60 days. As the age increased, the BSB developed structurally and functionally. Our findings provide a better understanding of splenic immune function and the pathogenesis of avian immunology in infectious diseases.


Assuntos
Barreira Hematoencefálica/fisiologia , Galinhas/imunologia , Doenças Transmissíveis/imunologia , Células Endoteliais/fisiologia , Estágios do Ciclo de Vida/fisiologia , Doenças das Aves Domésticas/imunologia , Baço/imunologia , Animais , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Imunidade , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
5.
Artigo em Inglês | MEDLINE | ID: mdl-31069176

RESUMO

The family of cell surface (cs-) mucins are constitutively expressed at the cell surface by nearly all epithelial cells, beneath the gel-mucin layer. All cs-mucin family members have structural features that enable them to act as a releasable decoy barrier to mucosal pathogens, by providing ligands for pathogen binding and the ability to shed the bound extracellular domain. Due to the towering structure of cs-mucins at the surface, binding of mucosal pathogens can also sterically block binding to underlying cellular receptors. The cytoplasmic tail domain of cs-mucins are capable of initiating signal transduction cascades and due to their conservation across species, may play an important biological role in cellular signaling. MUC1 is one of the most extensively studied of the cs-mucin family. With respect to its physiological function in the mucosal environment, MUC1 has been demonstrated to play a dynamic role in protection of the host from infection by a wide variety of pathogens and to regulate inflammatory responses to infection. This review briefly summarizes the current knowledge and new findings regarding the structural features relating to the function of MUC1, its role as a protective barrier against pathogen invasion and mechanisms by which this cs-mucin regulates inflammation.


Assuntos
Doenças Transmissíveis/imunologia , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Fatores Imunológicos/metabolismo , Mucina-1/metabolismo , Animais , Humanos
6.
Immunity ; 50(5): 1132-1148, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31117010

RESUMO

Helping B cells and antibody responses is a major function of CD4+ T cells. It has been 10 years since the publication of Bcl6 as the lineage-defining transcription factor for T follicular helper (Tfh) differentiation and the requirement of Tfh cells as the specialized subset of CD4+ T cells needed for germinal centers (the microanatomical sites of B cell mutation and antibody affinity maturation) and related B cell responses. A great deal has been learned about Tfh cells in the past 10 years, particularly regarding their roles in a surprising range of diseases. Advances in the understanding of Tfh cell differentiation and function are discussed, as are the understanding of Tfh cells in infectious diseases, vaccines, autoimmune diseases, allergies, atherosclerosis, organ transplants, and cancer. This includes discussion of Tfh cells in the human immune system. Based on the discoveries to date, the next decade of Tfh research surely holds many more surprises. VIDEO ABSTRACT.


Assuntos
Linfócitos B/imunologia , Centro Germinativo/imunologia , Linfócitos T Auxiliares-Indutores/citologia , Linfócitos T Auxiliares-Indutores/imunologia , Aterosclerose/imunologia , Doenças Autoimunes/imunologia , Diferenciação Celular/imunologia , Doenças Transmissíveis/imunologia , Humanos , Hipersensibilidade/imunologia , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo
7.
Microbiol Spectr ; 7(2)2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30953434

RESUMO

Human immune system (HIS) mice are created by transplanting human immune cells or their progenitor cells into highly immunodeficient recipient mouse hosts, thereby "humanizing" their immune systems. Over past decades, the field of HIS mice has evolved rapidly, as modifications of existing immunodeficient mouse strains have been developed, resulting in increasing levels of human tissue engraftment as humanization is optimized. Current HIS mouse models not only permit elevated levels of human cell engraftment but also demonstrate graft stability. As such, HIS mice are being extensively used to study the human innate and adaptive immune response against microbial infections in vivo. Compared to nonhumanized animal models, which are frequently infected with surrogate or adapted microbes, the HIS mouse models allow the analysis of interactions between human immune cells and bona fide pathogenic microbes, making them a more clinically relevant model. This article reviews the development of HIS mice and covers the different strategies used to humanize mice, as well as discussing the use of HIS mice for studying bacterial infections that cause human disease.


Assuntos
Doenças Transmissíveis/imunologia , Sistema Imunitário/imunologia , Imunidade Adaptativa , Animais , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos SCID , Transplante Heterólogo
8.
J Immunol Res ; 2019: 8303648, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949518

RESUMO

Vaccines are recognized worldwide as one of the most important tools for combating infectious diseases. Despite the tremendous value conferred by currently available vaccines toward public health, the implementation of additional vaccine platforms is also of key importance. In fact, currently available vaccines possess shortcomings, such as inefficient triggering of a cell-mediated immune response and the lack of protective mucosal immunity. In this regard, recent work has been focused on vaccine delivery systems, as an alternative to injectable vaccines, to increase antigen stability and improve overall immunogenicity. In particular, novel strategies based on edible or intradermal vaccine formulations have been demonstrated to trigger both a systemic and mucosal immune response. These novel vaccination delivery systems offer several advantages over the injectable preparations including self-administration, reduced cost, stability, and elimination of a cold chain. In this review, the latest findings and accomplishments regarding edible and intradermal vaccines are described in the context of the system used for immunogen expression, their molecular features and capacity to induce a protective systemic and mucosal response.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Absorção Cutânea , Vacinação/métodos , Vacinas de Plantas Comestíveis , Vacinas/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Administração Oral , Animais , Ensaios Clínicos como Assunto , Doenças Transmissíveis/imunologia , Técnicas de Transferência de Genes , Humanos , Imunidade Celular , Imunidade nas Mucosas/imunologia , Imunogenicidade da Vacina , Camundongos , Vacinas/imunologia
9.
Lupus ; 28(5): 629-634, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31027463

RESUMO

OBJECTIVE: The objective of this study was to determine whether characteristics of positive results in the indirect immunofluorescence assay on HEp-2 cells for anti-cell antibodies (HEp-2 IFA) differ between patients with non-autoimmune diseases (NADs) and patients with systemic autoimmune rheumatic diseases (SARDs). METHODS: Cross-sectional observational study comparing HEp-2 IFA test results in three groups: (a) 558 NAD patients comprising four subgroups (cancer ( n = 95), infectious diseases ( n = 148), psychiatric diseases ( n = 163), common non-infectious chronic diseases ( n = 152)); (b) 194 SARD patients; (c) 1217 healthy individuals (HIs). Sera were tested at 1:80 dilution and diluted to the end titer. Slides were analyzed by two independent blinded examiners. RESULTS: A positive HEp-2 IFA test occurred in 102 (18.3%) NAD patients, 170 (87.6%) SARD patients and 150 (12.3%) HIs. The four NAD subgroups did not differ regarding HEp-2 IFA frequency, titer or pattern. HEp-2 IFA titer was higher in NAD patients than in HIs and both had lower titer than SARD patients. Nuclear dense fine speckled pattern was more frequent in NAD patients and HIs than in SARD patients ( p < 0.001). Nuclear homogeneous and nuclear coarse speckled patterns were more frequent in SARD patients than in the other groups ( p < 0.001). The nuclear fine speckled pattern was prevalent in all three groups, but presented a gradient in titer across them; HIs and NAD patients had low and intermediary titers, which were significantly lower than in SARD patients ( p < 0.001). CONCLUSION: Positive HEp-2 IFA frequency, pattern and titer present differential features in NAD and SARD patients, and this attribute adds value to the test in the diagnosis of SARDs.


Assuntos
Anticorpos Antinucleares/sangue , Doenças Autoimunes/imunologia , Técnica Indireta de Fluorescência para Anticorpo , Doenças Reumáticas/imunologia , Adulto , Doenças Autoimunes/diagnóstico , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/imunologia , Estudos Transversais , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/imunologia , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/imunologia , Doenças Reumáticas/diagnóstico
10.
BMC Med ; 17(1): 75, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30961604

RESUMO

BACKGROUND: Comorbidity patterns of childhood infections, atopic diseases, and adverse childhood experiences (ACE) are related to immune system programming conditions. The aim of this study was to make a step beyond the hygiene hypothesis and to comprehensively classify these patterns with latent class analysis (LCA). A second aim was to characterize the classes by associations with immunological, clinical, and sociodemographic variables. METHODS: LCA was applied to data from the CoLaus|PsyCoLaus study (N = 4874, age range 35-82 years) separately for men and women. It was based on survey information on chickenpox, measles, mumps, rubella, herpes simplex, pertussis, scarlet fever, hay fever, asthma, eczema, urticaria, drug allergy, interparental violence, parental maltreatment, and trauma in early childhood. Subsequently, we examined how immune-mediated classes were reflected in leukocyte counts, inflammatory markers (IL-1ß, IL-6, TNF-α, hsCRP), chronic inflammatory diseases, and mental disorders, and how they differed across social classes and birth cohorts. RESULTS: LCA results with five classes were selected for further analysis. Latent classes were similar in both sexes and were labeled according to their associations as neutral, resilient, atopic, mixed (comprising infectious and atopic diseases), and ACE class. They came across with specific differences in biomarker levels. Mental disorders typically displayed increased lifetime prevalence rates in the atopic, the mixed, and the ACE classes, and decreased rates in the resilient class. The same patterns were apparent in chronic inflammatory diseases, except that the ACE class was relevant specifically in women but not in men. CONCLUSIONS: This is the first study to systematically determine immune-mediated classes that evolve early in life. They display characteristic associations with biomarker levels and somatic and psychiatric diseases occurring later in life. Moreover, they show different distributions across social classes and allow to better understand the mechanisms beyond the changes in the prevalence of chronic somatic and psychiatric diseases.


Assuntos
Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/imunologia , Hipótese da Higiene , Fenômenos do Sistema Imunológico/fisiologia , Análise de Classes Latentes , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/epidemiologia , Asma/imunologia , Criança , Comorbidade , Feminino , Humanos , Inflamação/complicações , Inflamação/epidemiologia , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Múltiplas Afecções Crônicas/epidemiologia , Prevalência , Inquéritos e Questionários
11.
Int J Mol Sci ; 20(7)2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30965568

RESUMO

Emerging evidence suggests that platelets, cytoplasmic fragments derived from megakaryocytes, can no longer be considered just as mediators in hemostasis and coagulation processes, but as key modulators of immunity. Platelets have received increasing attention as the emergence of new methodologies has allowed the characterization of their components and functions in the immune continuum. Platelet activation in infectious and allergic lung diseases has been well documented and associated with bacterial infections reproduced in several animal models of pulmonary bacterial infections. Direct interactions between platelets and bacteria have been associated with increased pulmonary platelet accumulation, whereas bacterial-derived toxins have also been reported to modulate platelet function. Recently, platelets have been found extravascular in the lungs of patients with asthma, and in animal models of allergic lung inflammation. Their ability to interact with immune and endothelial cells and secrete immune mediators makes them one attractive target for biomarker identification that will help characterize their contribution to lung diseases. Here, we present an original review of the last advances in the platelet field with a focus on the contribution of platelets to respiratory infections and allergic-mediated diseases.


Assuntos
Plaquetas/fisiologia , Doenças Transmissíveis/imunologia , Doenças Transmissíveis/metabolismo , Pneumopatias/imunologia , Pneumopatias/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Animais , Plaquetas/metabolismo , Humanos
12.
Nat Biotechnol ; 37(5): 527-530, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30936561

RESUMO

Oral antibodies that interfere with gastrointestinal targets and can be manufactured at scale are needed. Here we show that a single-gene-encoded monomeric immunoglobulin A (IgA)-like antibody, composed of camelid variable single domain antibodies (VHH) fused to IgA Fc (mVHH-IgA), prevents infection by enterotoxigenic Escherichia coli (F4-ETEC) in piglets. The mVHH-IgA can be produced in soybean seeds or secreted from the yeast Pichia pastoris, freeze- or spray-dried and orally delivered within food.


Assuntos
Doenças Transmissíveis/tratamento farmacológico , Gastroenteropatias/tratamento farmacológico , Imunoglobulina A/uso terapêutico , Anticorpos de Domínio Único/uso terapêutico , Administração Oral , Animais , Doenças Transmissíveis/imunologia , Doenças Transmissíveis/microbiologia , Escherichia coli/patogenicidade , Alimentos , Gastroenteropatias/imunologia , Gastroenteropatias/prevenção & controle , Gastroenteropatias/veterinária , Humanos , Imunoglobulina A/imunologia , Anticorpos de Domínio Único/imunologia , Suínos
13.
Front Immunol ; 10: 110, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30814993

RESUMO

Traditional vaccine development builds on the assumption that healthy individuals have virtually unlimited antigen recognition repertoires of receptors in B cells and T cells [the B cell receptor (BCR) and TCR respectively]. However, there are indications that there are "holes" in the breadth of repertoire diversity, where no or few B or T cell are able to bind to a given antigen. Repertoire diversity may in these cases be a limiting factor for vaccine efficacy. Assuming that it is possible to predict which B and T cell receptors will respond to a given immunogen, vaccine strategies could be optimized and personalized. In addition, vaccine testing could be simplified if we could predict responses through sequencing BCR and TCRs. Bulk sequencing has shown putatively specific converging sequences after infection or vaccination. However, only single cell technologies have made it possible to capture the sequence of both heavy and light chains of a BCR or the alpha and beta chains the TCR. This has enabled the cloning of receptors and the functional validation of a predicted specificity. This review summarizes recent evidence of converging sequences in infectious diseases. Current and potential future applications of single cell technology in immune repertoire analysis are then discussed. Finally, possible short- and long- term implications for vaccine research are highlighted.


Assuntos
Linfócitos B/imunologia , Doenças Transmissíveis/imunologia , Receptores de Antígenos de Linfócitos B/genética , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T/imunologia , Vacinas/imunologia , Animais , Controle de Doenças Transmissíveis , Humanos , Imunidade , Medicina de Precisão , Vacinação
14.
Transplant Proc ; 51(2): 512-516, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30879579

RESUMO

BACKGROUND: A significant gap exists between demand and supply of organs for patients with end-stage renal disease. To increase the donor pool, kidney transplantation is performed across ABO- and HLA-incompatible barriers. ABO-incompatible kidney transplant (ABOi-KT) recipients are at increased risk of antibody-mediated rejection, infection, and mortality. Hypogammaglobulinemia secondary to immunosuppression is highly prevalent after solid organ transplantation, and intravenous immunoglobulin (IVIG) has been reported to reduce the risks of infections in various settings. We use high-dose IVIG in ABOi-KT recipients perioperatively. We aimed to determine the rate of infectious complications along with graft and patient survival in our ABOi-KT recipients. METHODS: We included all adult patients who underwent ABOi-KT from the year 2007 to 2016. Patients received rituximab, plasma exchange, and IVIG (2 g/kg body weight). Thymoglobulin and intravenous methylprednisolone were used as induction treatment. Oral prednisone, mycophenolate mofetil, and tacrolimus were used as maintenance therapy. RESULTS: A total of 77 ABOi-KTs were performed, and the recipients were followed up for a median of 1557 days. Two patients were diagnosed as having BK nephropathy. No patients were diagnosed as having pneumocystis infection, cytomegalovirus disease, herpes simplex, varicella zoster, or fungal infection. One-year graft and patient survival was 94.8% and 100%, respectively. CONCLUSIONS: In our series of ABOi-KTs, we observed a low risk of infectious complications and excellent patient survival. High-dose IVIG might have reduced infections.


Assuntos
Sistema do Grupo Sanguíneo ABO , Incompatibilidade de Grupos Sanguíneos , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/imunologia , Transplante de Rim/métodos , Adulto , Feminino , Rejeição de Enxerto , Humanos , Hospedeiro Imunocomprometido/efeitos dos fármacos , Hospedeiro Imunocomprometido/imunologia , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade
15.
Neurochem Int ; 126: 36-58, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30862493

RESUMO

Prenatal and early childhood infections have been implicated in autism. Many autism susceptibility genes (206 Autworks genes) are localised in the immune system and are related to immune/infection pathways. They are enriched in the host/pathogen interactomes of 18 separate microbes (bacteria/viruses and fungi) and to the genes regulated by bacterial toxins, mycotoxins and Toll-like receptor ligands. This enrichment was also observed for misregulated genes from a microarray study of leukocytes from autistic toddlers. The upregulated genes from this leukocyte study also matched the expression profiles in response to numerous infectious agents from the Broad Institute molecular signatures database. They also matched genes related to sudden infant death syndrome and autism comorbid conditions (autoimmune disease, systemic lupus erythematosus, diabetes, epilepsy and cardiomyopathy) as well as to estrogen and thyrotropin responses and to those upregulated by different types of stressors including oxidative stress, hypoxia, endoplasmic reticulum stress, ultraviolet radiation or 2,4-dinitrofluorobenzene, a hapten used to develop allergic skin reactions in animal models. The oxidative/integrated stress response is also upregulated in the autism brain and may contribute to myelination problems. There was also a marked similarity between the expression signatures of autism and Alzheimer's disease, and 44 shared autism/Alzheimer's disease genes are almost exclusively expressed in the blood-brain barrier. However, in contrast to Alzheimer's disease, levels of the antimicrobial peptide beta-amyloid are decreased and the levels of the neurotrophic/myelinotrophic soluble APP alpha are increased in autism, together with an increased activity of α-secretase. sAPPα induces an increase in glutamatergic and a decrease in GABA-ergic synapses creating and excitatory/inhibitory imbalance that has also been observed in autism. A literature survey showed that multiple autism genes converge on APP processing and that many are able to increase sAPPalpha at the expense of beta-amyloid production. A genetically programmed tilt of this axis towards an overproduction of neurotrophic/gliotrophic sAPPalpha and underproduction of antimicrobial beta-amyloid may explain the brain overgrowth and myelination dysfunction, as well as the involvement of pathogens in autism.


Assuntos
Peptídeos beta-Amiloides/imunologia , Precursor de Proteína beta-Amiloide/imunologia , Transtorno Autístico/imunologia , Doenças Transmissíveis/imunologia , Leucócitos/imunologia , Transcriptoma/fisiologia , Peptídeos beta-Amiloides/genética , Precursor de Proteína beta-Amiloide/genética , Transtorno Autístico/epidemiologia , Transtorno Autístico/genética , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/genética , Predisposição Genética para Doença/genética , Humanos
16.
Nat Rev Genet ; 20(7): 377-388, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30737492

RESUMO

The derivation of induced pluripotent stem cells (iPSCs) over a decade ago sparked widespread enthusiasm for the development of new models of human disease, enhanced platforms for drug discovery and more widespread use of autologous cell-based therapy. Early studies using directed differentiation of iPSCs frequently uncovered cell-level phenotypes in monogenic diseases, but translation to tissue-level and organ-level diseases has required development of more complex, 3D, multicellular systems. Organoids and human-rodent chimaeras more accurately mirror the diverse cellular ecosystems of complex tissues and are being applied to iPSC disease models to recapitulate the pathobiology of a broad spectrum of human maladies, including infectious diseases, genetic disorders and cancer.


Assuntos
Doenças Transmissíveis/terapia , Doenças Genéticas Inatas/terapia , Células-Tronco Pluripotentes Induzidas/citologia , Modelos Biológicos , Neoplasias/terapia , Engenharia Tecidual/métodos , Animais , Diferenciação Celular , Linhagem da Célula/genética , Linhagem da Célula/imunologia , Quimera/genética , Quimera/imunologia , Doenças Transmissíveis/genética , Doenças Transmissíveis/imunologia , Doenças Transmissíveis/patologia , Descoberta de Drogas/métodos , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/imunologia , Doenças Genéticas Inatas/patologia , Terapia Genética/métodos , Humanos , Células-Tronco Pluripotentes Induzidas/imunologia , Células-Tronco Pluripotentes Induzidas/transplante , Modelos Animais , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/patologia , Organoides/citologia , Organoides/efeitos dos fármacos , Organoides/imunologia , Transplante de Tecidos/métodos , Transplante Heterólogo
17.
Front Immunol ; 10: 92, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30761149

RESUMO

The lungs represent a complex immune setting, balancing external environmental signals with a poised immune response that must protect from infection, mediate tissue repair, and maintain lung function. Innate lymphoid cells (ILCs) play a central role in tissue repair and homeostasis, and mediate protective immunity in a variety of mucosal tissues, including the lung. All three ILC subsets are present in the airways of both mice and humans; and ILC2s shown to have pivotal roles in asthma, airway hyper-responsiveness, and parasitic worm infection. The involvement of ILC3s in respiratory diseases is less well-defined, but they are known to be critical in homeostasis, infection and inflammation at other mucosal barriers, such as the gut. Moreover, they are important players in the IL17/IL22 axis, which is key to lung health. In this review, we discuss the emerging role of ILC3s in the context of infectious and inflammatory lung diseases, with a focus on data from human subjects.


Assuntos
Imunidade Inata , Pneumopatias/imunologia , Linfócitos/imunologia , Animais , Doenças Autoimunes/imunologia , Doenças Transmissíveis/imunologia , Doenças Transmissíveis/microbiologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Homeostase/imunologia , Humanos , Interleucina-17/metabolismo , Interleucinas/metabolismo , Linfócitos/classificação , Camundongos
18.
Front Immunol ; 10: 111, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30761152

RESUMO

T cell "exhaustion" describes a state of late-stage differentiation usually associated with active prevention of functionality via ligation of negative signaling receptors on the cell surface, and which can be reversed by blocking these interactions. This contrasts with T cell "senescence," which has been defined as a state that is maintained by intrinsic internal cell signaling (caused by DNA damage or other stresses) and which can be reversed pharmacologically. Interventions to alleviate these two different categories of inhibitory pathways may be desirable in immunotherapy for cancer and possibly certain infectious diseases, but reciprocally inducing and maintaining these states, or some properties thereof, may be beneficial in organ transplantation and autoimmunity. Even under physiological non-pathological conditions, T cell exhaustion and senescence may play a role in the retention of T cell clones required for immunosurveillance, and prevent their loss via elimination at the Hayflick limit. This essay briefly reviews T cell exhaustion in contrast to replicative senescence, and circumstances under which their modulation may be beneficial.


Assuntos
Linfócitos T CD4-Positivos/fisiologia , Linfócitos T CD8-Positivos/fisiologia , Senescência Celular , Encurtamento do Telômero/imunologia , Autoimunidade , Células Clonais , Doenças Transmissíveis/imunologia , Epigênese Genética , Humanos , Imunoterapia , Monitorização Imunológica , Neoplasias/imunologia , Neoplasias/terapia , Transplante de Órgãos , Receptor de Morte Celular Programada 1/metabolismo , beta-Galactosidase/metabolismo
19.
Nano Lett ; 19(3): 1914-1921, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30724085

RESUMO

Vaccination represents one of the most effective means of preventing infectious disease. In order to maximize the utility of vaccines, highly potent formulations that are easy to administer and promote high patient compliance are desired. In the present work, a biomimetic self-propelling micromotor formulation is developed for use as an oral antivirulence vaccine. The propulsion is provided by a magnesium-based core, and a biomimetic cell membrane coating is used to detain and neutralize a toxic antigenic payload. The resulting motor toxoids leverage their propulsion properties in order to more effectively elicit mucosal immune responses. After demonstrating the successful fabrication of the motor toxoids, their uptake properties are shown in vitro. When delivered to mice via an oral route, it is then confirmed that the propulsion greatly improves retention and uptake of the antigenic material in the small intestine in vivo. Ultimately, this translates into markedly elevated generation of antibody titers against a model toxin. This work provides a proof-of-concept highlighting the benefits of active oral delivery for vaccine development, opening the door for a new set of applications, in which biomimetic motor technology can provide significant benefits.


Assuntos
Antígenos/administração & dosagem , Antivirais/administração & dosagem , Biomimética , Doenças Transmissíveis/terapia , Administração Oral , Animais , Antígenos/imunologia , Antivirais/imunologia , Doenças Transmissíveis/imunologia , Doenças Transmissíveis/patologia , Humanos , Imunidade nas Mucosas/efeitos dos fármacos , Magnésio/química , Camundongos , Toxoides/metabolismo , Toxoides/toxicidade , Vacinação/métodos
20.
J Immunoassay Immunochem ; 40(1): 109-122, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30663510

RESUMO

Traditionally, definitive diagnosis of infectious diseases is made by cultivation of the causative agent, while various antigens and antibodies as biomarkers of various diseases are detected by commercially available ELISA kits. PCR has emerged as a major innovation that greatly accelerated the accumulation of genomic and transcriptomic data, yet it has also revolutionized microbial diagnostics by enabling the detection of pathogen nucleic acid. Despite the advantages of and vast experience in ELISA and PCR, the next generation research and diagnostic tools have to fulfill the requirements of systems and synthetic biology era. Multiplex bead assays hold this promise by providing a more complete multi-parametric picture of the biological phenomenon of interest at a fraction of time, sample volume and cost required for conventional assay systems. To date, numerous multiplex bead assays have been described to detect multiple antigen, antibody and nucleic acid targets of both microbial pathogens and immune response. These assays have been successfully used in diagnostic, cohort screening and research setups.


Assuntos
Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/imunologia , Testes Diagnósticos de Rotina/métodos , Doenças Transmissíveis/microbiologia , Testes Diagnósticos de Rotina/tendências , Humanos
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