ABSTRACT
The IGRA (Interferon Gamma Release Assays) test is currently the standard specific test for Mycobacterium tuberculosis infection status. However, a positive test cannot distinguish between active tuberculosis disease (ATBD) and latent tuberculosis infection (LTBI). Developing a test with this characteristic is needed. We conducted longitudinal studies to identify a combination of antigen peptides and cytokines to discriminate between ATBD and LTBI. We studied 54 patients with ATBD disease and 51 with LTBI infection. Cell culture supernatant from cells stimulated with overlapping Mycobacterium tuberculosis novel peptides and 40 cytokines/chemokines were analyzed using the Luminex technology. To summarize longitudinal measurements of analyte levels, we calculated the area under the curve (AUC). Our results indicate that in vitro cell stimulation with a novel combination of peptides (Rv0849-12, Rv2031c-14, Rv2031c-5, and Rv2693-06) and IL-1RA detection in culture supernatants can discriminate between LTBI and ATBD.
ABSTRACT
Malaria affects 228 million people worldwide each year, causing severe disease and worsening the conditions of already vulnerable populations. In this review, we explore how malaria has been detected in the past and how it can be detected in the future. Our primary focus is on finding new directions for low-cost diagnostic methods that unspecialized personnel can apply in situ. Through this review, we show that microfluidic devices can help pre-concentrate samples of blood infected with malaria to facilitate the diagnosis. Importantly, these devices can be made cheaply and be readily deployed in remote locations.
ABSTRACT
RESUMEN Objetivo: desarrollar un sistema microfluídico (lab-on-a-chip) para la detección de células tumorales circulantes de cáncer de mama (CTCs). Materiales y métodos: se diseñó el dispositivo en 3D y se fabricó usando fotolitografía suave y una cortadora láser. Se evaluó el funcionamiento del sistema y del arreglo magnético usando células Jurkat y células de cáncer de mama que poseen diferente expresión de los marcadores superficiales CD45 y EpCAM. Los anticuerpos contra los marcadores fueron unidos a perlas magnéticas. Adicionalmente se usaron nanopartículas de hierro para evaluar su atrapamiento. Resultados: las nanopartículas lograron atraparse de manera significativa en el área propuesta por el modelamiento de campos magnéticos. Las células tumorales marcadas con los anticuerpos magnéticos quedaron atrapadas. Conclusiones: se logró fabricar un lab-on-a-chip capaz de atrapar CTCs generando una excelente herramienta de diagnóstico y de análisis de la progresión de la enfermedad.
ABSTRACT Objective. to develop a microfluidic system (lab-on-a-chip) for detecting circulating breast cancer tumor cells. Materials and methods . the device was designed using 3D technology, and it was manufactures using soft photolithography and a laser cutting machine. The system performance and its magnetic settings were assessed using Jurkat cells and breast cancer cells that show different expression of CD45 and EpCAM surface markers. Antibodies against these markers were bound to magnetic pellets. Additionally, iron nanoparticles were used for assessing their entrapment. Results . nanoparticles were significantly trapped in the area set by magnetic field modeling. Tumor cells labeled with magnetic antibodies became trapped. Conclusions . we were able to manufacture a lab-on-a-chip system that is capable to trap circulating breast cancer tumor cells, which may become an excellent tool for diagnosis and follow-up for this condition.
ABSTRACT
BACKGROUND: Guillain-Barre Syndrome (GBS) is considered a complex disorder with significant environmental effect and genetic susceptibility. Genetic polymorphisms in CD1E, CD1A, IL-17, and/or ICAM1 had been proposed as susceptibility genetic variants for GBS mainly in Caucasian population. This study explores the association between selected polymorphisms in these genes and GBS susceptibility in confirmed GBS cases reported in mestizo population from northern Peru during the most recent GBS outbreak of May 2018. METHODS: A total of nine nonrelated cases and 11 controls were sequenced for the polymorphic regions of CD1A, CD1E, IL-17, and ICAM1. RESULTS: We found a significant protective association between heterozygous GA genotype in ICAM1 (241Gly/Arg) and GBS (p < .047). IL-17 was monomorphic in both controls and patients. No significant differences were found in the frequency of SNPs in CD1A and CD1E between the group with GBS patients and healthy controls. CONCLUSION: ICAM1 polymorphisms might be considered as potential genetic markers of GBS susceptibility. Further studies with larger sample size will be required to validate these findings.
Subject(s)
Antigens, CD1/genetics , Guillain-Barre Syndrome/pathology , Intercellular Adhesion Molecule-1/genetics , Interleukin-17/genetics , Aged , Body Mass Index , Case-Control Studies , Female , Genetic Predisposition to Disease , Genotype , Guillain-Barre Syndrome/genetics , Humans , Male , Middle Aged , Peru , Polymorphism, Single Nucleotide , Regression Analysis , Risk FactorsABSTRACT
Chemokines are a burgeoning family of chemotactic cytokines displaying a broad array of functions such as regulation of homeostatic leukocyte traffic and development, as well as activating the innate immune system. Their role in controlling early and late inflammatory stages is now well recognized. An improper balance either in chemokine synthesis or chemokine receptor expression contributes to various pathological disorders making chemokines and their receptors a useful therapeutic target. Research in this area is progressing rapidly, and development of novel agents based on chemokine/ chemokine receptors antagonist functions are emerging as attractive alternative drugs. Some of these novel agents include generation of chemokine-derived peptides (CDP) with potential agonist and antagonist effects on inflammation, cancer and against bacterial infections. CDP have been generated mainly from N- and C-terminus chemokine sequences with subsequent modifications such as truncations or elongations. In this review, we present a glimpse of the different pharmacological actions reported for CDP and our current understanding regarding the potential use of CDP alone or as part of the novel therapies proposed in the treatment of microbial infections and cancer.
Subject(s)
Anti-Infective Agents/pharmacology , Antineoplastic Agents/pharmacology , Chemokines/pharmacology , Peptide Fragments/pharmacology , Animals , Anti-Infective Agents/chemistry , Antineoplastic Agents/chemistry , Chemokines/chemistry , Humans , Peptide Fragments/chemistryABSTRACT
La piel constituye la primera barrera del sistema inmune contra potenciales agentes patógenos y nocivos externos. Evidencia importante sugiere que las células inmunológicas requieren de funciones conjuntas con los queratinocitos, para alertar y ensamblar una respuesta inmune adecuada, que incluye la formación del sistema de alerta denominado inflamosoma. Adicionalmente, nuevos fenotipos funcionales de células presentadoras de antígenos (CPA) en la piel como las células dendríticas han demostrado tener gran importancia en ensamblar la respuesta inmune incluso mayor que las células T circulantes. La primera entrega de este artículo describe la funcionalidad de los queratinocitos y las células dendriticas en la piel, para en la segunda parte discriminar sus roles juntos a los linfocitos T y las fallas de la regulación durante las interacciones en la formaión del inflamosoma.
Human skin is the first shield which provides essential protection of the human body from injury and infection. Important evidence reinforces the importance of keratinocytes as sensors of danger through alert systems such as the inflammasome and key components in the appropriate immune response. In addition, newly identified antigen-presenting cells (APCs), as dendritic cells, have demonstrated to have a key role of assembling the immune response even major than circulating T cells in skin. The first part of this review focuses on dissecting the functional role of keratinocytes and dendritic cells in skin in order to, in the second part, analyze their roles and interactions together with the T lymphocytes during the inflammasome formation.
Subject(s)
Antigen-Presenting Cells/immunology , Keratinocytes , Keratinocytes/immunologyABSTRACT
Clásicamente, el vitiligo ha sido definido como una enfermedad de la piel en la cual los melanocitos (MC) son erradicados de una epidermis lesionada por células T autorreactivas con la presencia de moléculas del sistema inmune y otros componentes no inmunológicos que resultan en la pérdida de pigmento y lesiones cutáneas en el paciente. Anteriormente, la ausencia y daño en los MC ha sido asociado a mayor riesgo de cáncer de piel incluyendo melanoma. Sin embargo, en vitiligo se ha identificado la presencia de melanocitos 'no pigmentados', similar a individuos albinos, que aparentemente confieren mayor resistencia para el desarrollo de melanoma en estas personas. Estos hechos aparentemente contradictorios se complican aún más cuando los antigenos de los MC reconocidos por el sistema inmune durante la respuesta autoinmune o en la inmunidad antitumoral son los mismos en ambas enfermedades. Un análisis de las similitudes y diferencias entre la respuesta inmune contra MC observada en vitiligo y su rol en la inmunidad tumoral observada en melanoma, podría llevar a entender mejor el rol de estas células y al futuro desarrollo de nuevas terapias para ambas enfermedades.
Classically, vitiligo has been defined as a skin disease in which melanocytes (MC) are eradicated from lesional epidermis by MC- reactive T cells, as well as other non-immune and immune components, resulting in disfiguring loss of pigmento Moreover, the absence 01' damage on MC has frequently been associated to a major risk to develop skin cancer including melanoma. However, patients with vitiligo have also shown 'non-pigmented' MC in epidermis similar to individuals with albinism, and these cells are apparently conferring resistance of developing melanoma. These seemingly contradictory facts are further complicated because, the MC antigens which are immunologically recognized are shared for both diseases producing fairly different results. An analysis of the similarities and differences between the autoimmunity observed in vitiligo and the tumour immunity observed in melanoma might lead to a better understanding of the MC roles and the development of new therapies for both diseases.
Subject(s)
Autoimmunity , Melanocytes , Melanoma , Vitiligo/therapyABSTRACT
Los mastocitos y basófilos han demostrado tener múltiples funciones dentro del sistema inmune. Además de su clásico rol de respuesta inflamatoria en contra de alérgenos también se les ha visto participando en respuestas directas contra diversos agentes infecciosos. Diversas funciones in vivo de estas células han permanecido poco conocidas debido a la usencia de modelos animales que puedan investigar su desarrollo y su real importancia durante salud y enfermedad. Sin embargo, recientes estudios han podido caracterizar y aislar las células precursoras de estos linajes, y así entender nuevas funciones efectoras que eran desconocidas in vivo. Esta revisión brinda conceptos básicos e importantes del desarrollo y la acción efectora de estas células enfatizando conceptos inmunológicos necesarios para la comprensión de los mecanismos de enfermedad en diversos estados patológicos.
Mast cells and basophils have demonstrated to have both beneficial and detrimental functions for the immune system. Additionally to their classic role in pro-inflammatory responses to allergens, they are also involved directly in immunity against different pathogens. Because there are few anima/s models developed to investigate these cells in vivo, their functions during health and disease remain poorly understood. This review gives a short glance in the development and functional status of mast cells and basophils focusing on immunology concepts necessary to get a major understanding of the mechanisms of disease in different pathological states.
Subject(s)
Basophils , Immunity, Innate , Mast CellsABSTRACT
Interactions between tumour cells and microenvironments may affect their growth and metastasis formation. In search for a better understanding of the role of cellular mediators in the progression of cancer, we investigated the effect of pro-inflammatory cytokines IL-1, IL-6, TNF-alpha and IFN-gamma on the regulation of expression of chemokine receptors CXCR4, CXCR2, CX3CR1, CCR9, and CCR5 in the human breast cancer cell line MCF-7. Our results showed that IL-1 increased CXCR4 expression whereas TNF-alpha increased CX3CR1, CCR9 and CCR5. Interestingly, this regulation was not homogeneous, emphasizing the inherent heterogeneity in cancer that may be responsive to specific inflammatory microenvironments.
Subject(s)
Breast Neoplasms/immunology , Cytokines/immunology , Neoplasm Metastasis/immunology , Receptors, Chemokine/biosynthesis , Breast Neoplasms/pathology , Cell Line, Tumor , Chemotaxis/immunology , Female , Flow Cytometry , Humans , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Introducción: La enfermedad pulmonar inflamatoria crónica tiene como característica común el proceso de angiogénesis patológica. Recientes trabajos han relacionado a la adenosina, una molécula de señalización, y quimioquinas como reguladores de este proceso, aunque la relación y asociación entre estos factores no ha sido muy investigada. Objetivo: Determinar el papel de la adenosina en la angiogénesis sostenida en procesos pulmonares inflamatorios crónicos. Diseño: Experimental. Lugar: Bioterio del Grupo de Investigación en Inmunología de la Facultad de Medicina de la Universidad Nacional de San Agustín, Arequipa, Perú e Instituto de Investigaciones Biomédicas de la Universidad Nacional Autónoma de México. Material biológico: Ratones deficientes en adenosina deaminasa (ADA) de la cepa C57BL/6J. Métodos y procedimientos: Se evaluó la relación entre los niveles de adenosina en pulmón y la angiogénesis traqueal utilizando patrones morfométricos, además de la expresión de la quimioquina CXCL1 y su receptor mediante ensayos de PCR y Elisa. Principales medidas de resultados: Niveles de adenosina en pulmón, angiogénesis traqueal y expresión a CXCL1 y su receptor. Resultados: Se demostró un significativo incremento de angiogénesis relacionado a dosis elevadas de adenosina y una regresión importante del proceso al administrar ADA de reemplazo. Se encontró también niveles de CXCL1 elevados de manera dependiente a la adenosina, en los ratones deficientes. La neutralización in vivo del receptor de CXCL1 (mCXCR2) mostró una marcada inhibición de la acción angiogénica. Conclusión: Nuestros hallazgos sugieren que la adenosina juega un rol importante en la inducción de angiogénesis pulmonar vía CXCL1/CXCR2, en la enfermedad pulmonar crónica.
Introduction: Chronic lung disease's feature is pathological angiogenesis, a still little understood process in this and other diseases. Recently adenosine, a signaling molecule, and chemokines have been considered regulators of this process. Though, relationship between these factors has not been investigated. Objective: To determine the role of adenosine in the induction of angiogenesis during pulmonary chronic inflammation. Design: Experimental. Setting: Bioterio, Immunology Research Group, Facultad de Medicina, Universidad Nacional de San Agustin, Arequipa, Peru, and Biomedical Research Institute, Universidad Nacional Autonoma de Mexico. Biologic material: C57BL/6J adenosine deaminase (ADA)-deficient mice. Methods and interventions: By morphometric analysis we determined relationship between adenosine levels in lung and tracheal angiogenesis, and expression to CXCL1 and its receptor by PCR and Elisa assays. Main outcome measures: Lung adenosine levels, tracheal angiogenesis, and expression to CXCL1 and its receptor. Results: We demonstrated a significant increase of angiogenesis related to high doses of adenosine and an important inhibition of the process when we administered replacement ADA. In the ADA-deficient mice CXCL1 levels rose depending on adenosine levels. CXCL1 receptor (CXCR2) in vivo neutralization showed dramatic inhibition of angiogenic activity. Conclusions: Adenosine may play an important role, via CXCL1/CXCR2, in the induction of pulmonary angiogenesis in pulmonary chronic disease.