RESUMEN
Cellular metabolic dysregulation is a consequence of SARS-CoV-2 infection that is a key determinant of disease severity. However, how metabolic perturbations influence immunological function during COVID-19 remains unclear. Here, using a combination of high-dimensional flow cytometry, cutting-edge single-cell metabolomics, and re-analysis of single-cell transcriptomic data, we demonstrate a global hypoxia-linked metabolic switch from fatty acid oxidation and mitochondrial respiration towards anaerobic, glucose-dependent metabolism in CD8+Tc, NKT, and epithelial cells. Consequently, we found that a strong dysregulation in immunometabolism was tied to increased cellular exhaustion, attenuated effector function, and impaired memory differentiation. Pharmacological inhibition of mitophagy with mdivi-1 reduced excess glucose metabolism, resulting in enhanced generation of SARS-CoV-2- specific CD8+Tc, increased cytokine secretion, and augmented memory cell proliferation. Taken together, our study provides critical insight regarding the cellular mechanisms underlying the effect of SARS-CoV-2 infection on host immune cell metabolism, and highlights immunometabolism as a promising therapeutic target for COVID-19 treatment.
Asunto(s)
COVID-19 , Humanos , SARS-CoV-2 , Linfocitos T CD8-positivos , Tratamiento Farmacológico de COVID-19RESUMEN
RESUMEN: En el año 2013, se publicó un artículo acerca de lo realizado en Chile en temas de protección radiológica en cardiología intervencionista (CI) pediátrica. A continuación se muestra el trabajo de continuidad realizado en los últimos 8 años, destacando los principales resultados alcanzados y proponiendo mejoras en la seguridad y protección radiológica en esta práctica clínica. Desde el año 2013 se han seguido evaluando en términos de dosis de radiación y calidad de imagen, los sistemas de rayos X utilizados en Chile para procedimientos de CI pediátricos y, en particular, los equipos de los servicios de los Hospitales Luis Calvo Mackenna y Roberto del Rio. Se han medido las tasas de dosis de radiación dispersa a la posición habitual de los ojos y tobillos de los cardiólogos que operan los equipos de rayos X. También contamos con un conjunto de "Niveles de Referencia para Diagnóstico" clasificados por rangos de edad y peso, junto con la estimación de valores de dosis por órgano y dosis efectiva para los pacientes. Podemos afirmar que, actualmente, contamos con una metodología consolidada para caracterizar, en términos de dosis y calidad de imagen, los sistemas de rayos X. Sin embargo, sigue pendiente actualizar la normativa nacional que regula el uso seguro de las radiaciones ionizantes en medicina, como también aspectos de formación en protección radiológica para el personal médico implicado.
ABSRSCT: An article on the status of radiological protection during procedures of interventional cardiology in pediatric patients in Chile was published in 2013. The present article relates the continuing efforts to improve radiological protection highlighting their results and proposing additional measures to improve radiological protection during the procedure. Since 2013 we have continued the evaluation of radiation doses, image quality, and X Ray systems used in Chile. We have measured diffused radiation dose at operator´s eye and ankle levels to elaborate a "Reference guide" according to patient´s age and weight. However, we still lack a national regulatory norm for the X Ray systems to be used and for the appropriate training of those involved in procedures of interventional cardiology in pediatric patients.
Asunto(s)
Humanos , Pediatría , Protección Radiológica/métodos , Medidas de Seguridad/tendencias , Chile , DosimetríaRESUMEN
Allogeneic bone marrow transplantation (BMT) is an effective therapy for hematological malignancies due to the graft-versus-leukemia (GVL) effect to eradicate tumors. However, its application is limited by the development of graft-versus-host disease (GVHD), a major complication of BMT. GVHD is evoked when T-cells in the donor grafts recognizealloantigen expressed by recipient cells and mount unwanted immunological attacks against recipient healthy tissues. Thus, traditional therapies are designed to suppress donor T-cell alloreactivity. However, these approaches substantially impair the GVL effect so that the recipient's survival is not improved. Understanding the effects of therapeutic approaches on BMT, GVL, and GVHD, is thus essential. Due to the antigen-presenting and cytokine-secreting capacities to stimulate donor T-cells, recipient dendritic cells (DCs) play a significant role in the induction of GVHD. Therefore, targeting recipient DCs becomes a potential approach for controlling GVHD. This work provides a description of a novel BMT platform to investigate how host DCs regulate GVH and GVL responses after transplantation. Also presented is an effective BMT model to study the biology of GVHD and GVL after transplantation.
