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1.
Artigo em Inglês | MEDLINE | ID: mdl-31618376

RESUMO

Dermatophytosis is a cutaneous mycosis caused by a plethora of keratinophilic fungi, but Trichophyton rubrum is the most common etiological agent. Despite its high prevalence worldwide, little is known about the host defense mechanisms in this infection, particularly the in situ immune response. Using an immunohistochemistry approach, we investigated the density of CD1a+, factor XIIIa+ and CD68+ cells in the skin of dermatophytosis patients. Langerhans cells (CD1a+ cells) were significantly decreased in the epidermis of patients, both in affected and unaffected areas. In the dermis, however, no differences in the density of macrophages (CD68+ cells) and dermal dendrocytes (factor XIIIa+ cells) were observed. These results suggest that the decreased number of Langerhans cells may be a risk factor for development of dermatophytosis.


Assuntos
Dermatomicoses/imunologia , Dermatomicoses/patologia , Imunidade Inata/imunologia , Células de Langerhans/imunologia , Células de Langerhans/patologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Tinha/imunologia , Tinha/patologia , Adulto Jovem
2.
Adv Exp Med Biol ; 1172: 21-62, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31628650

RESUMO

Molecules encoded by the Major Histocompatibility Complex (MHC) bind self or foreign peptides and display these at the cell surface for recognition by receptors on T lymphocytes (designated T cell receptors-TCR) or on natural killer (NK) cells. These ligand/receptor interactions govern T cell and NK cell development as well as activation of T memory and effector cells. Such cells participate in immunological processes that regulate immunity to various pathogens, resistance and susceptibility to cancer, and autoimmunity. The past few decades have witnessed the accumulation of a huge knowledge base of the molecular structures of MHC molecules bound to numerous peptides, of TCRs with specificity for many different peptide/MHC (pMHC) complexes, of NK cell receptors (NKR), of MHC-like viral immunoevasins, and of pMHC/TCR and pMHC/NKR complexes. This chapter reviews the structural principles that govern peptide/MHC (pMHC), pMHC/TCR, and pMHC/NKR interactions, for both MHC class I (MHC-I) and MHC class II (MHC-II) molecules. In addition, we discuss the structures of several representative MHC-like molecules. These include host molecules that have distinct biological functions, as well as virus-encoded molecules that contribute to the evasion of the immune response.


Assuntos
Imunidade Adaptativa , Imunidade Inata , Complexo Principal de Histocompatibilidade , Receptores de Antígenos de Linfócitos T , Linfócitos T , Imunidade Adaptativa/imunologia , Animais , Humanos , Imunidade Inata/imunologia , Complexo Principal de Histocompatibilidade/imunologia , Receptores de Antígenos de Linfócitos T/química , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Células Matadoras Naturais/química , Receptores de Células Matadoras Naturais/imunologia , Linfócitos T/imunologia
3.
Isr Med Assoc J ; 21(7): 454-459, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31507120

RESUMO

BACKGROUND: Platelets have the ability to influence the immune system and the inflammatory process and may be strongly involved in the whole pathogenic process of chronic inflammatory joint diseases, such as rheumatoid arthritis. They may play a significant role even before the clinical onset of the disease, contributing to the loss of tolerance of the immune system and the induction of autoimmunity. Subsequently, they can interact with the most important cellular players involved in autoimmunity and inflammation, namely innate immunity cells and T cells and eventually contribute to the building of inflammation in the synovium, thus inducing the activation, migration, and proliferation of fibroblasts that eventually lead to joint damage. Due to their peculiar features, studying the behavior of platelets is a challenging task; however, platelets may prove to be valuable therapeutic targets in the future.


Assuntos
Artrite Reumatoide/imunologia , Plaquetas/imunologia , Sinovite/imunologia , Artrite Reumatoide/patologia , Autoimunidade/imunologia , Fibroblastos/imunologia , Humanos , Imunidade Inata/imunologia , Inflamação/imunologia , Inflamação/patologia , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Sinovite/patologia , Linfócitos T/imunologia
4.
Vet Parasitol ; 273: 36-44, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31442891

RESUMO

Rhipicephalus (Boophilus) microplus ticks cause major constraints to public and livestock health, and serious economic losses. It is well known that the immune response to infestations with cattle ticks is influenced by the host genetic background leading to distinct immunological profiles between bovine hosts genetically susceptible and resistant. The influence of Bos indicus (Bi) and Bos taurus (Bt) maternal lineage ancestry of mitochondrial DNA in the profile of the immune response of Zebu cattle to ticks remains unknown. The present work evaluated the hematological parameters and the immune response profile in the peripheral blood of a Guzerat dairy herd, further categorized into two maternal lineage ancestry subgroups (Bi-mtDNA and Bt-mtDNA) after experimental infestation with larvae of R. microplus. Our data demonstrated that although hematological and erythrogram analysis showed a similar profile throughout, some cell populations present a distinct profile between the groups. Especially MON, CD335+ and CD8+ T-cells are predominant in Bi-mtDNA. Moreover, an overall picture of R. microplus infestation demonstrated that Bi-mtDNA presented a more efficient and earlier innate immune response. Bi-mtDNA showed a greater number of connections with R. microplus counts and also with the CD25+ activation marker of the immune response. Bi-mtDNA showed greater number of connections, with an important participation of the innate immune while Bt-mtDNA showed a delay in the immune response. Elucidating the mechanisms by which resistant animals prevent heavy tick infestation is a crucial step in the development of predictive biomarkers for tick resistance for use in selective breeding programs, and is also potentially useful for the development of anti-tick vaccines.


Assuntos
Doenças dos Bovinos/imunologia , Interações Hospedeiro-Parasita/imunologia , Imunidade Inata/imunologia , Rhipicephalus/imunologia , Infestações por Carrapato/veterinária , Animais , Cruzamento , Bovinos , DNA Mitocondrial/genética , Indústria de Laticínios , Feminino , Perfilação da Expressão Gênica , Linfócitos T/imunologia , Infestações por Carrapato/imunologia
5.
Scand J Immunol ; 90(5): e12804, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31267559

RESUMO

Immune checkpoint inhibitors are among the newest, cutting-edge methods for the treatment of cancer. Currently, they primarily influence T cell adaptive immunotherapy targeting the PD-1/PD-L1 and CTLA-4/B7 signalling pathways. These inhibitors fight cancer by reactivating the patient's own adaptive immune system, with good results in many cancers. With the discovery of the "Don't Eat Me" molecule, CD47, antibody-based drugs that target the macrophage-related innate immunosuppressive signalling pathway, CD47-SIRPα, have been developed and have achieved stunning results in the laboratory and the clinic, but there remain unexplained instances of tumour immune escape. While investigating the immunological tolerance of cancer to anti-CD47 antibodies, a second "Don't Eat Me" molecule on tumour cells, beta 2 microglobulin (ß2m), a component of MHC class I, was described. Some tumour cells reduce their surface expression of MHC class I to escape T cell recognition. However, other tumour cells highly express ß2m complexed with the MHC class I heavy chain to send a "Don't Eat Me" signal by binding to leucocyte immunoglobulin-like receptor family B, member 1 (LILRB1) on macrophages, leading to a loss of immune surveillance. Investigating the mechanisms underlying this immunosuppressive MHC class I-LILRB1 signalling axis in tumour-associated macrophages will be useful in developing therapies to restore macrophage function and control MHC class I signalling in patient tumours. The goal is to promote adaptive immunity while suppressing the innate immune response to tumours. This work will identify new therapeutic targets for the development of pharmaceutical-based tumour immunotherapy.


Assuntos
Antígenos CD/imunologia , Tolerância Imunológica/imunologia , Receptor B1 de Leucócitos Semelhante a Imunoglobulina/imunologia , Neoplasias/terapia , Evasão Tumoral/imunologia , Microglobulina beta-2/imunologia , Imunidade Adaptativa/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Imunidade Inata/imunologia , Macrófagos/imunologia , Transdução de Sinais/imunologia , Linfócitos T/imunologia
7.
Med Mycol ; 57(Supplement_3): S294-S306, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31292656

RESUMO

Invasive fungal infections (IFIs) occur predominantly in immunocompromised individuals but can also be seen in previously well persons. The human innate immune system recognizes key components of the fungal cell wall as foreign resulting in a myriad of signaling cascades. This triggers release of antifungal molecules as well as adaptive immune responses, which kill or at least contain the invading fungi. However, these defences may fail in hosts with primary or secondary immunodeficiencies resulting in IFIs. Knowledge of a patient's immune status enables the clinician to predict the fungal infections most likely to occur. Moreover, the occurrence of an opportunistic mycosis in a patient without known immunocompromise usually should prompt a search for an occult immune defect. A rapidly expanding number of primary and secondary immunodeficiencies associated with mycoses has been identified. An investigative approach to determining the nature of these immunodeficiencies is suggested to help guide clinicians encountering patients with IFI. Finally, promising adjunctive immunotherapy measures are currently being investigated in IFI.


Assuntos
Imunidade Inata/imunologia , Infecções Fúngicas Invasivas/imunologia , Humanos , Hospedeiro Imunocomprometido/imunologia , Infecções Oportunistas/imunologia
8.
Yakugaku Zasshi ; 139(7): 993-998, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31257258

RESUMO

Prion diseases, including human Creutzfeldt-Jakob disease, are infectious, intractable central neurodegenerative diseases, which are also zoonoses that commonly infect not only higher organisms but also a wide variety of animals. Pathogenic prions induce abnormal prion protein (PrP), which is produced by structural conversion of normal PrP, a beta-sheet-rich structure with high aggregation propensity. Thus, it is believed that the host is immunotolerant against prions because there is no difference in the primary structure of normal and abnormal PrP, and prions do not induce a marked immune response. Recently, using mutated Toll-like receptor (TLR) 4-transgenic mice, a bioassay after prion inoculation has intriguingly found that the TLR4-signaling pathway may have a protective role against prion infection. Meanwhile, we reported that a transcription factor, interferon regulatory factor-3 (IRF-3), located downstream of TLR4 signaling, showed resistance to prions. IRF-3-inducing type I interferon (I-IFN) is a critical factor for the host defense against pathogen invasion. These findings indicate that the TLR-signaling pathway of the innate immune system might regulate prion invasion. However, the details have not been fully determined. In this symposium, we will introduce new findings including the relationship between I-IFN and prions.


Assuntos
Imunidade Inata/imunologia , Doenças Priônicas/imunologia , Proteínas Priônicas/imunologia , Animais , Síndrome de Creutzfeldt-Jakob , Humanos , Fator Regulador 3 de Interferon , Interferon Tipo I , Camundongos , Transdução de Sinais/imunologia , Receptor 4 Toll-Like/imunologia , Zoonoses
9.
Arch Anim Nutr ; 73(1): 44-51, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31274343

RESUMO

The study evaluated the effects of different doses of 25-hydroxyvitamin D3 (25(OH)D3) on growth performance, immune function and antioxidative capacity in piglets. In a 21-d trial, 35 weaned pigs were divided into five groups and diets were supplemented with 5.5 (control), 43.0, 80.5, 118.0 and 155.5 µg 25(OH)D3/kg, respectively. No treatment effects were observed for average daily gain, average daily feed intake and feed to gain ratio. Increasing dietary 25(OH)D3 levels increased serum 25(OH)D3 concentrations linearly (p < 0.01), decreased the frequency of CD3+CD4+ and CD3+CD8+ T cells (p < 0.01), and the serum level of complement component 3 (p < 0.05). Supplementation of 80.5 and 118.0 µg 25(OH)D3/kg enhanced the activity of serum glutathione peroxidase (p < 0.05) and addition of 43.0 µg 25(OH)D3/kg increased the malondialdehyde concentration (p < 0.05). Overall, feeding high-dose 25(OH)D3 to weaned pigs partly improved immune functions and the antioxidative capacity.


Assuntos
Antioxidantes/metabolismo , Calcifediol/metabolismo , Imunidade Inata/imunologia , Sus scrofa/fisiologia , Vitaminas/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Calcifediol/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Imunidade Inata/efeitos dos fármacos , Sus scrofa/crescimento & desenvolvimento , Sus scrofa/imunologia , Vitaminas/administração & dosagem , Desmame
10.
Mol Immunol ; 112: 223-232, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31177059

RESUMO

The complement system is a major component of innate immunity playing essential roles in the destruction of pathogens, the clearance of apoptotic cells and immune complexes, the enhancement of phagocytosis, inflammation, and the modulation of adaptive immune responses. During the last decades, numerous studies have shown that the complement system has key functions in the biology of certain tissues. For example, complement contributes to normal brain and embryonic development and to the homeostasis of lipid metabolism. However, the complement system is subjected to the effective balance between activation-inactivation to maintain complement homeostasis and to prevent self-injury to cells or tissues. When this control is disrupted, serious pathologies eventually develop, such as C3 glomerulopathy, autoimmune conditions and infections. Another heterogeneous group of ultra-rare diseases in which complement abnormalities have been described are the lipodystrophy syndromes. These diseases are characterized by the loss of adipose tissue throughout the entire body or partially. Complement over-activation has been reported in most of the patients with acquired partial lipodystrophy (also called Barraquer-Simons Syndrome) and in some cases of the generalized variety of the disease (Lawrence Syndrome). Even so, the mechanism through which the complement system induces adipose tissue abnormalities remains unclear. This review focuses on describing the link between the complement system and certain forms of lipodystrophy. In addition, we present an overview regarding the clinical presentation, differential diagnosis, classification, and management of patients with lipodystrophy associated with complement abnormalities.


Assuntos
Complemento C3/imunologia , Lipodistrofia/imunologia , Tecido Adiposo/imunologia , Animais , Complexo Antígeno-Anticorpo/imunologia , Humanos , Imunidade Inata/imunologia
11.
Nat Commun ; 10(1): 2377, 2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-31147550

RESUMO

Glycans from microbial pathogens are well known pathogen-associated molecular patterns that are recognized by the host immunity; however, little is known about whether and how mammalian self-glycans activate the host immune response, especially in the context of autoimmune disease. Using biochemical fractionation and two-dimensional HPLC, we identify an abundant and bioactive free glycan, the Manß1-4GlcNAc disaccharide in TREX1-associated autoimmune diseases. We report that both monosaccharide residues and the ß1-4 linkage are critical for bioactivity of this disaccharide. We also show that Manß1-4GlcNAc is produced by oligosaccharyltransferase hydrolysis of lipid-linked oligosaccharides in the ER lumen, followed by ENGase and mannosidase processing in the cytosol and lysosomes. Furthermore, synthetic Manß1-4GlcNAc disaccharide stimulates a broad immune response in vitro, which is in part dependent on the STING-TBK1 pathway, and enhances antibody response in vivo. Together, our data identify Manß1-4GlcNAc as a novel innate immune modulator associated with chronic autoimmune diseases.


Assuntos
Doenças Autoimunes/imunologia , Autoimunidade/imunologia , Dissacarídeos/imunologia , Imunidade Inata/imunologia , Proteínas de Membrana/imunologia , Proteínas Serina-Treonina Quinases/imunologia , Animais , Doenças Autoimunes/genética , Modelos Animais de Doenças , Retículo Endoplasmático , Exodesoxirribonucleases/genética , Fibroblastos , Camundongos , Fosfoproteínas/genética , Células RAW 264.7
12.
Life Sci ; 231: 116593, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31228512

RESUMO

Inflammasomes are the major mechanistic complexes that include members of the NOD-like receptor (NLRs) or AIM2-like receptors (ALRs) families, which are affiliated with the innate immune system. Once NLRs or ALRs are activated by pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), the caspase-1 or -11 is activated by binding with NLRs or ALRs via its own unique cytosolic domains. As a result, caspase-1 or -11 enhances the production of IL-1ß and IL-18, which results in inflammation via the recruitment of immune cells, such as macrophages, and the promotion of programmed cell death mechanisms such as pyroptosis. In addition, the consistent cascades of inflammasomes would precede both minor and severe autoimmune diseases and cancers. The clinical relevance of inflammasomes in multiple forms of cancer highlights their therapeutic promise as molecular targets. To closely analyze the physiological roles of inflammasomes in cancers, here, we describe the fundamental knowledge regarding the current issues of inflammasomes in relevant cancers, and discuss possible therapeutic values in targeting these inflammasomes for the prevention and treatment of cancer.


Assuntos
Inflamassomos/metabolismo , Inflamassomos/fisiologia , Neoplasias/terapia , Alarminas/metabolismo , Animais , Apoptose/fisiologia , Doenças Autoimunes/imunologia , Proteínas de Transporte/metabolismo , Caspase 1/metabolismo , Caspases/metabolismo , Humanos , Imunidade Inata/imunologia , Inflamação/imunologia , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Proteínas NLR/fisiologia , Padrões Moleculares Associados a Patógenos/metabolismo , Transdução de Sinais
13.
Mol Immunol ; 111: 136-144, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31054407

RESUMO

Production of antimicrobial peptides cathelicidins, interferons and cytokines is an important feature in airway epithelial host defense. The innate immune response to alpha-herpesvirus infection at the sites of primary replication has not been fully studied. Thus, the aim of this study was to determine the expression of innate immune components, cathelicidins, IFNß, TNFα and TNF receptors (TNFRI and TNFRII) during acute infection and reactivation of bovine herpesvirus type 1 (BoHV-1) and 5 (BoHV-5) in the respiratory tract and lymphoid tissue of their natural host. We found that BoHV infection modulates mainly the expression of BMAP28, a key cathelicidin in cattle. It was downregulated by both viruses in retropharyngeal lymph nodes of acutely infected-calves, and it was accompanied by a lower expression of IFNß, TNFα and TNFRI. BoHV-5 showed a pronounced role in the downregulation of BMAP28, even in nasal mucosa and lung. However, during reactivation, BoHV-5 upregulated both BMAP28 and IFNß in retropharyngeal lymph nodes. Acute replication induced also TNFα mRNA and protein synthesis, and expression of TNFRI and II was positively regulated during both acute infection and reactivation, particularly in the trachea. Moreover, BMAP27 was detected during BoHV-1 reactivation suggesting a potential role at this stage. Thus, cathelicidins are implicated in alpha-herpesvirus infections of the bovine respiratory system and the response is distinct during BoHV-1 and BoHV-5 acute infection and reactivation. This demonstrates that these viruses modulate differentially the components of innate immune response, possibly influencing their pathogenesis. This study provides an initial pilot analysis of factors that might be implicated in alpha-herpesvirus infection of the bovine respiratory system.


Assuntos
Catelicidinas/imunologia , Doenças dos Bovinos/imunologia , Infecções por Herpesviridae/imunologia , Herpesvirus Bovino 1/imunologia , Interferon beta/imunologia , Fator de Necrose Tumoral alfa/imunologia , Animais , Bovinos , Citocinas/imunologia , Infecções por Herpesviridae/veterinária , Imunidade Inata/imunologia , Projetos Piloto , RNA Mensageiro/imunologia , Receptores do Fator de Necrose Tumoral/imunologia , Sistema Respiratório/imunologia , Sistema Respiratório/virologia , Regulação para Cima/imunologia
14.
Fish Shellfish Immunol ; 91: 122-129, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31055018

RESUMO

Selenium (Se) is a micronutrient that becomes toxic when present at higher concentrations in fish tissues. Allium mongolicum Regel flavonoids (AMRF) have been documented to possess antioxidant, immunoenhancement and anti-inflammation properties. The aim of this study was to investigate the protective effects and potential mechanisms of dietary supplementation of AMRF and Se exposure on oxidative stress, immune responses and immune-related genes expression in Channa argus. A total of 480 C. argus were randomly divided into eight groups housed in twenty-four 200 L glass aquarium (3 tanks per group, 20 fish per tank). The fish were exposed for 56 days to waterborne Se at 0, 50, 100 and 200 µg/L and/or dietary AMRF at 40 mg/kg. The result indicated that AMRF exerted significant protective effects by preventing alterations in the levels of bioaccumulation, malondialdehyde, lysozyme, complement C3 and immunoglobulin M. AMRF also assists in the elevation of catalase and glutathione peroxidase in the liver and spleen while regulating the expression of immune-related genes including NF-κB p65, IκB-α, TNF-α, IL-1ß, IL-8, HSP70, HSP90, and glucocorticoid receptor after 56 days of Se exposure. Our results suggest that administration of AMRF (40 mg/kg) has the potential to combat Se toxicity in C. argus.


Assuntos
Allium/química , Peixes/imunologia , Flavonoides/farmacologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/imunologia , Estresse Oxidativo , Selênio/metabolismo , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Distribuição Aleatória , Testes de Toxicidade Subcrônica
15.
Mol Immunol ; 112: 10-21, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31075558

RESUMO

Extracellular adenosine triphosphate (eATP), released following inflammatory stimulation or infection, is a potent signaling molecule in activating innate immune responses in fish. However, the regulation of eATP-mediated innate immunity in fish remains unknown. Ecto-nucleoside triphosphate diphosphohydrolase 1 (CD39) is a critical molecular switch for controlling the ATP levels in the extracellular space. CD39 plays a key role in regulating eATP-activated innate immune responses through the phosphohydrolysis of pro-inflammatory eATP to inactive AMP. Here, we identified and characterized a CD39 homolog (namely, poCD39) in the Japanese flounder Paralichthys olivaceus and analyzed its regulatory role in eATP-mediated innate immunity. Real-time quantitative PCR analysis revealed that poCD39 is ubiquitously present in all tested normal tissues with dominant expression in enriched Japanese flounder head kidney macrophages (HKMs). Immune challenge experiments demonstrated that poCD39 expression was upregulated by inflammatory stimulation and Edwardsiella tarda infection. Biochemical and immunofluorescence analysis revealed that poCD39 is a functional glycosylated membrane protein for the hydrolysis of eATP. Inhibition of poCD939 activity with the ecto-NTPDase inhibitor ARL 67156 resulted in increased IL-1beta gene expression and ROS production in Japanese flounder HKMs. In contrast, overexpression of poCD39 in Japanese flounder FG-9307 cells reduced eATP-induced pro-inflammatory cytokine IL-1beta gene expression. Finally, poCD39 expression was significantly induced by eATP stimulation in the HKMs, suggesting that eATP may provide a feedback mechanism for transcriptional regulation of fish CD39. Taken together, we identified and characterized a functional fish CD39 protein involved in regulating eATP-mediated innate immune responses in fish.


Assuntos
Trifosfato de Adenosina/imunologia , Antígenos CD/imunologia , Apirase/imunologia , Linguado/imunologia , Imunidade Inata/imunologia , Monofosfato de Adenosina/imunologia , Animais , Edwardsiella tarda/imunologia , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/veterinária , Proteínas de Peixes/imunologia , Linguado/microbiologia , Regulação da Expressão Gênica/imunologia , Rim Cefálico/imunologia , Rim Cefálico/microbiologia , Inflamação/imunologia , Inflamação/microbiologia , Japão , Macrófagos/imunologia , Macrófagos/microbiologia , Espécies Reativas de Oxigênio/imunologia , Transcrição Genética/imunologia , Regulação para Cima/imunologia
16.
Hum Cell ; 32(3): 231-239, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31079327

RESUMO

Innate lymphoid cells (ILCs) are a recently described group of innate immune cells that mirror the characteristics of CD4+ T cell subsets. Based on their transcriptional factor and cytokine profile, ILCs family is divided into main subgroups-ILC1s, ILC2s, and ILC3s. Recently, one new subpopulation of ILCs with immunosuppressive characteristics has been described and named as regulatory ILCs. Various roles of ILCs have been confirmed including the role during the response to microbial signals, the role in inflammation and process of tissue repair. Function of ILCs is mediated through the cytokines production and direct cell-to-cell contact. This article summarizes in detail, the relationship between the ILCs and various immune-related disorders.


Assuntos
Doenças do Sistema Imunitário/imunologia , Imunidade Inata/imunologia , Linfócitos/imunologia , Linfócitos T CD4-Positivos/imunologia , Citocinas/metabolismo , Humanos , Tolerância Imunológica , Inflamação/imunologia
17.
Scand J Immunol ; 90(2): e12776, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31069824

RESUMO

The number of the X chromosome-linked genes has been previously suggested to influence immune responses and the development of autoimmune diseases. In the present study, we aimed at evaluating the level of expression of CD40L (an X-linked gene involved in adaptive immunity) and TLR7 (an X-linked gene involved in innate immunity) in a variety of different karyotypes. Those included males, females and patients with X chromosome aneuploidy. Healthy females (46, XX; n = 10) and healthy males (46, XY; n = 10) were compared to females with Turner syndrome (TS) (45, X; n = 11) and males with Klinefelter syndrome (KS) (47, XXY; n = 5). Stimulation of peripheral blood mononuclear cells (PBMCs) with PMA and ionomycin resulted in higher percentage of CD3 + CD40L+ T cells (P < 0.001) and higher level expression of CD40L in T cell (P < 0.001) in female and KS patients compared with male and TS patients. TLR7-mediated IFN-alpha production by HLADR + CD3- CD19- cells was significantly upregulated in healthy women compared with healthy males, TS and KS patients (P < 0.001). TLR7 agonist-stimulated PBMCs from healthy females and KS patients expressed significantly higher levels of TLR7 mRNA than those from male and TS patients (P < 0.05). The increased expression of the X-linked genes TLR7 and CD40L in healthy females and KS patients suggests that the presence of two X chromosomes plays a major role in enhancing both innate and adaptive immune responses. These results may contribute to the explanation of sex-based differences in immune biology and the sex bias in predisposition to autoimmune diseases.


Assuntos
Imunidade Adaptativa/genética , Ligante de CD40/biossíntese , Ligante de CD40/genética , Cromossomos Humanos X/genética , Dosagem de Genes/genética , Imunidade Inata/genética , Receptor 7 Toll-Like/biossíntese , Receptor 7 Toll-Like/genética , Imunidade Adaptativa/imunologia , Antígenos CD19/biossíntese , Complexo CD3/biossíntese , Células Cultivadas , Variações do Número de Cópias de DNA/genética , Feminino , Humanos , Imunidade Inata/imunologia , Interferon-alfa/biossíntese , Ionomicina/farmacologia , Síndrome de Klinefelter/genética , Leucócitos Mononucleares/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Masculino , Ácidos Polimetacrílicos/farmacologia , RNA Mensageiro/biossíntese , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Síndrome de Turner/genética
18.
Life Sci ; 229: 173-179, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31103606

RESUMO

AIMS: The innate immune response induced by bacterial peptidoglycan peptides, such as γ-d-glutamyl-meso-diaminopimelic acid (iE-DAP), is an important host defense system. However, little is known about the innate immune response in the lung alveolar region. In this study, we examined induction of the innate immune response by iE-DAP in human alveolar epithelial cell lines, NCI-H441 (H441) and A549. MAIN METHODS: Induction of the innate immune response was evaluated by measuring the mRNA expression of cytokines and their release into the culture medium. KEY FINDINGS: iE-DAP treatment increased the mRNA expression of interleukin (IL)-6 and IL-8, and increased release of these pro-inflammatory cytokines into the culture medium in H441 cells, but not in A549 cells. Lack of release of these cytokines in A549 cells may have been due to lack of peptide transporter 2 (PEPT2) function. Intracellular nucleotide-binding oligomerization domain 1 (NOD1) recognizes iE-DAP and activates downstream signaling pathways to initiate the immune response. Therefore, the role of mitogen-activated protein kinase (MAPK) signaling pathways was examined in H441 cells. As a result of inhibition studies, receptor-interacting serine/threonine-protein kinase 2 and MAPK signaling pathways, such as p38 MAPK and extracellular signal-regulated kinase, but not c-Jun N-terminal kinase, were determined to be involved in the innate immune response in H441 cells. In addition, the nuclear factor κB pathway also played a role in the innate immune response. SIGNIFICANCE: These findings indicated that the innate immune response induced by bacterial peptides could occur in a PEPT2- and NOD1-dependent manner in alveolar epithelial cells.


Assuntos
Células Epiteliais Alveolares/imunologia , Ácido Diaminopimélico/análogos & derivados , Imunidade Inata/imunologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Simportadores/metabolismo , Células A549 , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/metabolismo , Citocinas/metabolismo , Ácido Diaminopimélico/farmacologia , Humanos , Imunidade Inata/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/genética , Transdução de Sinais , Simportadores/genética
19.
Int J Mol Sci ; 20(9)2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31072011

RESUMO

Group 2 innate lymphoid cells (ILC2) have emerged as a major component of type 2 inflammation in mice and humans. ILC2 secrete large amounts of interleukins 5 and 13, which are largely responsible for host protective immunity against helminth parasites because these cytokines induce profound changes in host physiology that include: goblet cell metaplasia, mucus accumulation, smooth muscle hypercontractility, eosinophil and mast cell recruitment, and alternative macrophage activation (M2). This review covers the initial recognition of ILC2 as a distinct cell lineage, the key studies that established their biological importance, particularly in helminth infection, and the new directions that are likely to be the focus of emerging work that further explores this unique cell population in the context of health and disease.


Assuntos
Helmintíase/imunologia , Helmintos/imunologia , Imunidade Inata/imunologia , Linfócitos/imunologia , Animais , Linhagem da Célula/imunologia , Helmintíase/parasitologia , Helmintos/patogenicidade , Humanos , Imunidade Inata/genética , Interleucina-13/genética , Interleucina-5/genética , Camundongos
20.
PLoS Pathog ; 15(5): e1007691, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31107917

RESUMO

Cyclic GMP-AMP synthase (cGAS) senses viral DNA in the cytosol and then catalyzes synthesis of the second messenger cGAMP, which activates the ER-localized adaptor protein Mediator of IRF3 Activator (MITA) to initiate innate antiviral response. Human cytomegalovirus (HCMV) proteins can antagonize host immune responses to promote latent infection. Here, we identified HCMV UL42 as a negative regulator of cGAS/MITA-dependent antiviral response. UL42-deficiency enhances HCMV-induced production of type I interferons (IFNs) and downstream antiviral genes. Consistently, wild-type HCMV replicates more efficiently than UL42-deficient HCMV. UL42 interacts with both cGAS and MITA. UL42 inhibits DNA binding, oligomerization and enzymatic activity of cGAS. UL42 also impairs translocation of MITA from the ER to perinuclear punctate structures, which is required for MITA activation, by facilitating p62/LC3B-mediated degradation of translocon-associated protein ß (TRAPß). These results suggest that UL42 can antagonize innate immune response to HCMV by targeting the core components of viral DNA-triggered signaling pathways.


Assuntos
Antivirais/farmacologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Imunidade Inata/imunologia , Proteínas de Membrana/metabolismo , Nucleotidiltransferases/metabolismo , Proteínas Virais/farmacologia , Citomegalovirus/efeitos dos fármacos , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/metabolismo , Infecções por Citomegalovirus/virologia , DNA Viral/genética , DNA Viral/metabolismo , Células HEK293 , Humanos , Proteínas de Membrana/genética , Nucleotidiltransferases/genética , Transdução de Sinais
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