Advances on efficacy and mechanism of vitamin D3 in adjuvant therapy of mycobacterium tuberculosis infection / 中华临床感染病杂志

Every year more than 10 million people newly infected with Mycobacterium tuberculosis (MTB) worldwide, which seriously threats human health and life. The anti-MTB infection drugs are constantly developed and updated. Vitamin D3 is a drug which can regulate the immune system, its effect on MTB infection has attracted more and more attention. This article reviews the clinical efficacy of vitamin D3 in adjuvant therapy for MTB infection, and its mechanism in regulating the innate and adaptive immune system, to provide insight for treatment of MTB infection.

Propiedades antioxidantes e inmunoestimulantes de polifenoles en peces carnívoros de cultivo / Antioxidant and immunostimulant properties of polyphenols in carnivorous farmed fish

Resumen El cultivo intensivo de peces es una estrategia econòmicamente importante para producir alimento. Sin embargo, las prácticas de cultivo intensivo generan estrés oxidativo e inmunosupresión, lo que ocasiona pérdidas de la calidad del especimen y aumento en la mortalidad. Para contrarrestar estos efectos, se ha optado por la administración de vegetales como fuente de polifenoles con propiedades antioxidantes e inmunoestimulantes en peces carnívoros de cultivo. El objetivo de este trabajo fue describir los efectos de los polifenoles de origen vegetal como antioxidantes e inmunoestimulantes en peces carnívoros, y promover su uso como ingredientes funcionales en la acuicultura. Los vegetales como fuente de polifenoles tienen la capacidad de mejorar los sistemas de defensa inmune y antioxidante de las especies analizadas, con un tejido de mejor calidad nutricional y un mayor contenido endógeno de antioxidantes. No obstante, las propiedades biológicas de los polifenoles dependen del tipo y concentra ción en el vegetal, de la dosis y el tiempo de administración, así como de la matriz alimentaria, la cual determina la bioaccesibilidad y biodisponibilidad de los polifenoles en el organismo. Es la información generada sobre el efecto de los polifenoles en la calidad post mortem, por lo que se deben realizar más estudios.

Abstract Fish production by intensive aquaculture, is an economically important strategy to produce food. However, intensive fish farming generates oxidative stress and suppress the immune system, causing loss of product quality and increasing fish mortality rates. To diminish these effects, plants as a source of polyphenols with antioxidants and immunostimulant properties were administered to carnivorous farmed fish. The aim of this study was to describe the effects of plant polyphenols as antioxidants and immunostimulants on carnivorous fish, and to promote their use as functional ingredients in aquaculture. Plants as a source of polyphenols showed the ability to improve the immune and antioxidant defense systems of the analyzed species, resulting in a tissue of better nutritional quality and a higher endogenous antioxidant content. However, the biological properties of polyphenols are dependent on the type of plant and their concentration within it, the dose and the time of administration, as well as the food matrix, which determines their bioaccessibility and bioavailability in the organism. There is little information on the effec of polyphenols in post mortem quality; therefore, further studies should be conducted.

Innate immunity and HPV: friends or foes

Most human papillomavirus infections are readily cleared by the host immune response. However, in some individuals, human papillomavirus can establish a persistent infection. The persistence of high-risk human papillomavirus infection is the major risk factor for cervical cancer development. These viruses have developed mechanisms to evade the host immune system, which is an important step in persistence and, ultimately, in tumor development. Several cell types, receptors, transcription factors and inflammatory mediators involved in the antiviral immune response are viral targets and contribute to tumorigenesis. These targets include antigen-presenting cells, macrophages, natural killer cells, Toll-like receptors, nuclear factor kappa B and several cytokines and chemokines, such as interleukins, interferon and tumor necrosis factor. In the present review, we address both the main innate immune response mechanisms involved in HPV infection clearance and the viral strategies that promote viral persistence and may contribute to cancer development. Finally, we discuss the possibility of exploiting this knowledge to develop effective therapeutic strategies.

Síndromes periódicos asociados a criopirina: etiopatogenia, características clínicas, diagnóstico y tratamiento / Cryopiryn-associated peryodic syndrome: etiopathogenesis, clinical features, diagnosis and treatment

Los desórdenes autoinflamatorios monogénicos comprenden un grupo de enfermedades caracterizadas por episodios recurrentes y espontáneos de fiebre e inflamación sistémica, en ausencia de infección, autoanticuerpos o células T específicas para antígenos propios (autorreactivas). Estas condiciones se deben a mutaciones en genes que codifican para proteínas que son claves en la regulación de la respuesta inflamatoria innata y se consideran como inmunodeficiencias primarias. Las enfermedades que comprenden estos síndromes representan un espectro clínico de diferentes mutaciones, con ganancia de función, de un gen denominado NLRP3 o CIAS1 que codifica para la proteína criopirina, de ahí que estos desórdenes sean también conocidos con el nombre de criopirinopatías. Dentro de estos se encuentran los síndromes periódicos asociados a criopirina que incluyen tres enfermedades: el síndrome autoinflamatorio familiar inducido por frío; el síndrome de Muckle-Wells y el síndrome crónico, infantil, neurológico, cutáneo y articular. Clínicamente se caracterizan por rash tipo urticariano, fiebre periódica, inflamación a nivel del sistema nervioso central, artropatía, manifestaciones oculares y riesgo de amiloidosis como complicación a largo plazo. La función clave de la criopirina en la liberación de la IL-β sugiere el criterio racional de implementar terapias anti-IL-1 para el tratamiento de estos síndromes. La administración de drogas como anakinra, canakinumab y rilonacept muestra un efecto marcado sobre el control de las manifestaciones inflamatorias, clínicas y de los parámetros de laboratorio en estos síndromes. Se describe la etiopatogenia de estas entidades, sus principales características clínicas, el diagnóstico y el tratamiento(AU)

Monogenic autoinflammatory disorders encompass a group of diseases characterized by spontaneous and recurring fever and systemic inflammation in the absence of infection, autoantibodies or specific T cells for self antigens (self-reactive). These conditions are caused by mutations in genes encoding proteins that play a key role in the regulation of innate inflammatory response and are considered primary immunodeficiencies. Diseases comprising these syndromes represent a different clinical spectrum of mutations, with gain of function of a gene called NLRP3 or CIAS1 encoding cryopyrin protein, hence these disorders are also known under the name cryopyrinpathies. Among these are the cryopyrin-associated periodic syndrome which include three conditions: familial cold autoinflammatory syndrome; Muckle-Wells syndrome and chronic infantile neurological, cutaneous and articular syndrome. In clinical terms, it is characterized by urticarial rash, periodic fever, inflammation of central nervous system (CNS), arthropathy, ocular manifestations and risk of amyloidosis as a long-term complication. The key role of cryopirin in the release of IL-β suggests rational approach to implement anti-IL-1 therapy for the treatment of these syndromes. The administration of drugs such as anakinra, canakinumab, and rilonacept shows a marked effect on the control of inflammatory manifestations, as well as clinical and laboratory parameters in these syndromes effect. The pathogenesis of these entities, as well as their main clinical features, diagnosis and treatment are described(AU)

Enfermedades autoinflamatorias / Autoinflammatory diseases

Las enfermedades autoinflamatorias monogénicas son desórdenes raros que resultan en defectos del sistema inmune innato, originando excesiva respuesta a señales de peligro, activación espontánea de vías inflamatorias o pérdida de reguladores inhibitorios. En los últimos 15 años un creciente número de enfermedades inflamatorias monogénicas han sido descriptas y sus respectivos genes responsables identificados. Las proteínas codificadas por estos genes están involucradas en las vías regulatorias de la inflamación y están expresadas fundamentalmente en las células del sistema inmune innato. Si bien un grupo de pacientes exhibe inflamación sistémica episódica (fiebres periódicas), estos desórdenes están mediados por una continua sobreproducción y liberación de mediadores pro-inflamatorios -especialmente la interleucina 1beta- y su conceptualización como enfermedades autoinflamatorias es preferible por sobre la de fiebres periódicas. Las enfermedades más frecuentes son fiebre mediterránea familiar (FMF), TRAPS, deficiencia de mevalonatocinasa/síndrome de hiper IgD (MKD/HIDS) y los síndromes periódicos asociados a criopirina (CAPS). Sus características clínicas frecuentemente incluyen fiebre, erupciones cutáneas, compromiso de serosas y reactantes de fase aguda. Los autoanticuerpos están usualmente ausentes pero pueden observarse en ciertos síndromes. El diagnóstico es clínico y se basa en las características fenotípicas. El diagnóstico genético es muy importante pero debe ser realizado de manera juiciosa e interpretado con cautela. El tratamiento con agentes biológicos que bloquean citocinas pro-inflamatorias, particularmente IL-1, ha demostrado ser efectivo en muchos pacientes. Sin embargo, en otros tantos casos no se descubren anormalidades genéticas y el tratamiento es subóptimo, planteando la posibilidad de mutaciones patogénicas en genes y vías aún no explorados.

The monogenic autoinflammatory diseases are rare, genetic disorders resulting in constitutive innate immune defects leading to excessive response to danger signals, spontaneous activation of inflammatory mediators or loss of inhibitory regulators. During the past 15 years, a growing number of monogenic inflammatory diseases have been described and their respective responsible genes identified. The proteins encoded by these genes are involved in the regulatory pathways of inflammation and are mostly expressed in cells of the innate immune system. Although a group of patients exhibit episodic systemic inflammation (periodic fevers), these disorders are mediated by continuous overproduction and release of pro-inflammatory mediators, notably IL-1β, and are best considered as autoinflammatory diseases rather than periodic fevers. The most common autoinflammatory diseases are familial Mediterranean fever (FMF), TNF receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency/hyperimmunoglobulin D syndrome (MKD/HIDS) and the cryopyrin-associated periodic syndromes (CAPS). Clinical features often include fever, cutaneous rash, serosal involvement and acute phase reactants. Autoantibodies are usually absent but may accompany certain syndromes. Diagnosis remains clinical and is based on the different phenotypic features. Genetic diagnosis is of utmost importance, but must be performed judiciously and interpreted cautiously. Treatment with biologic agents that block proinflammatory cytokines, particularly IL-1, has proved to be dramatically effective in many patients. Still, in many cases of autoinflammation no genetic abnormalities are detected and treatment remains suboptimal, raising the question of novel pathogenic mutations in unexplored genes and pathways.

Development and application of drugs targeting the innate and adaptive immune system in the colon / 中国药科大学学报

@#Recent advances in immunology and genetics have verified that the innate immune and adaptive immune responses that mediated by T cells, have been considered to play an important role in inducing inflammatory bowel disease. It’s difficult to cure the disease due to the complexity of the disease. However, the development and application of medicine, which target the immune response in the colon, attract great attention in recent years. In present, there are two types of targeting drugs in the intestinal immune systems: one of them targets the intestinal innate immune system, which includes targeting signal transduction, signal molecule and lymphocytes while the other targets adaptive immune system that includes inhibition of intenstinal T cell activation, differentiation and regulation of T cell cytokines and balance of T cell. This article mainly gives a comprehensive overview in four aspects, which include the intestinal innate immune response, adaptive immune response, drugs targeting in the intestinal innate and adaptive immune response. Furthermore, research directions are also pointed out in the review.

Recognition systemic juvenile idiopathic arthritis / 中华实用儿科临床杂志

Systemic juvenile idiopathic arthritis (sJIA) is systemic inflammatory disease classified as a subtype of juvenile idiopathic arthritis (JIA).Besides arthritis,it is characterised by systemic features such as spiking fever,skin rash,hepatosplenomegaly or serositis.It is becoming clear now that abnormalities in the innate immunity [cytokines such as interleukin (IL)-1,IL-6 and IL-18,and neutrophils and monocytes/macrophages rather than lymphocytes] play a major role in the pathogenesis of sJIA,distinguishing it from other JIA subtypes.Another distinctive feature of sJIA is its strong association with macrophage activation syndrome (MAS).Based on this,consensus is emerging that sJIA should be viewed as an autoinflammatory syndrome rather than a classic auto-immune disease.As a consequence of the progression in understanding the underlying mechanisms of sJIA,major changes in the management are evolving.Recently,remarkable improvement has been observed with IL-1 and IL-6 targeted therapies.These therapies might also change the long-term outcome of this disease.

Role of Cyclic GMP-AMP Synthase in Sensing Human Immunodeficiency Virus

Cyclic guanosine monophosphate adenosine monophosphate (cGAMP) synthase (cGAS) detects human immunodeficiency virus (HIV) and produces cGAMP to induce cytokines. Reverse transcribed DNA of HIV is critical for triggering innate immune responses as inhibitor of HIV reverse transcriptase blocked the induction of interferon-beta by the virus. Furthermore, knockout of cGAS in human or mouse cell lines abrogated the production of cytokines by HIV infection highlighting the essential role of cGAS in detection of HIV and other retroviruses.

Negative regulatory approaches to the attenuation of Toll-like receptor signaling

Toll-like receptors (TLRs) are pivotal components of the innate immune response, which is responsible for eradicating invading microorganisms through the induction of inflammatory molecules. These receptors are also involved in responding to harmful endogenous molecules and have crucial roles in the activation of the innate immune system and shaping the adaptive immune response. However, TLR signaling pathways must be tightly regulated because undue TLR stimulation may disrupt the fine balance between pro- and anti-inflammatory responses. Such disruptions may harm the host through the development of autoimmune and inflammatory diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Several studies have investigated the regulatory pathways of TLRs that are essential for modulating proinflammatory responses. These studies reported several pathways and molecules that act individually or in combination to regulate immune responses. In this review, we have summarized recent advancements in the elucidation of the negative regulation of TLR signaling. Moreover, this review covers the modulation of TLR signaling at multiple levels, including adaptor complex destabilization, phosphorylation and ubiquitin-mediated degradation of signal proteins, manipulation of other receptors, and transcriptional regulation. Lastly, synthetic inhibitors have also been briefly discussed to highlight negative regulatory approaches in the treatment of inflammatory diseases.

Toll-like receptors and their role in sepsis / 医学研究生学报

The Toll like receptors(TLRs)are essential transmembrane signaling receptors of the innate immune system that alert the host to the presence of a microbial invader.The recent discovery of the TLR has rapidly expanded our knowledge of molecular events that initiate host pathogen interactions.These functional attributes of the cellular receptors provide insights into the nature of pattern recognition receptors that activate the human antimicrobial defense systems.The fundamental significance of the TLR in the generation of systemic inflammation and the pathogenesis of septic shock is reviewed. The potential clinical implications of therapeutic modulation of these recently characterized receptors of innate immunity are also discussed.