TLR7 activation in M-CSF-dependent monocyte-derived human macrophages potentiates inflammatory responses and prompts neutrophil recruitment

1 p.-4 fig.Toll-like receptor 7 (TLR7) is an endosomal Pathogen-Associated Molecular Pattern (PAMP) receptor that senses single-stranded RNA (ssRNA) and whose engagement results in the production of type I IFN and pro-inflammatory cytokines upon viral exposure. Recent genetic studies have established that a dysfunctional TLR7-initiated signaling is directly linked to the development of SARS-CoV-2-induced severe COVID-19. We previously showed that TLR7 is preferentially expressed by macrophages generated in the presence of M-CSF (M-MØ), whose MAFB-dependent transcriptome resembles pathogenic pulmonary monocyte-derived macrophage subsets in severe COVID-19. We now report that TLR7 activation in M-MØ triggers a weak MAPK, NFkB and STAT1 activation and leads to defective production of type I IFN. Nonetheless, TLR7 engagement re-programs MAFB+ M-MØ towards a distinctive transcriptional profile. Specifically, TLR7-activated M-MØ acquired the expression of genes that characterize inflammatory macrophage subsets in COVID-19 and other inflammatory diseases, including genes encoding neutrophil-attracting chemokines (CXCL1-3, CXCL5, CXCL8) reported as biomarkers for severe COVID-19. Functionally, TLR7-activated M-MØ displayed enhanced proinflammatory responses towards secondary stimulation and a robust production of neutrophil-attracting chemokines (CXCL1, CXCL5, CXCL8), which was dependent on the transcription factors MAFB and AhR. Interestingly, CXCL1 and CXCL5 release from M-MØ was also promoted by SARS-CoV-2 but not by Virus-like particles. As defective TLR7 signaling and enhanced pulmonary neutrophil/lymphocyte ratio associate with severe COVID-19, these results suggest that targeting macrophage TLR7 might be a therapeutic strategy for viral infections where monocyte-derived macrophages exhibit a pathogenic role.This research work was also funded by the European Commission – NextGenerationEU (Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global)Peer reviewe

SaO2 as a predictor of exercise-induced hypoxemia in chronic obstructive pulmonary disease at moderate altitude

Background: Given the high prevalence of chronic obstructive pulmonary disease (COPD) in Bogota (2630 m above the sea), screening methods are required for COPD patients who develop exercise-induced hypoxemia (EIH). Objective: The objective was to measure the productive capacity of basal oxygen saturation for the detection of EIH during the 6-min walking test (6MWT) in patients diagnosed with COPD in a hospital in Bogotá. Design: This was a cross-sectional, retrospective study. Population: Patients diagnosed with COPD with SaO2≥88% who attended the Pneumology Section of the FSFB for a 6MWT between 2013 and 2017 were included in the study. Measurements: Age, sex, anthropometric data, SaO2, SaO2 during 6MWT, and spirometry were evaluated. Results: Ninety-two patients with EIH and 32 patients without EIH were studied. Statistically significant differences were found in SaO2, minimum SaO2 during 6MWT, and BMI (90.8% vs 93%, 80.3% vs 88.9%, and 26.7 kg/m2 vs 23.8 kg/m2, respectively). FEV1 was without statistically significant differences (74.1% vs 78.6%). The ROC curve showed a better cut-off point for detecting EIH with basal SaO2≤92% (sensitivity 76.1%, specificity 62.5%, NPV 47.6%, and PPV 85.4%) and SaO2≤94% as the best sensitivity point (sensitivity 94.6%, specificity 15.6%, NPV 76.3%, and PPV 50%). Conclusion: SaO2 is not a good screening test for EIH in COPD patients at moderate altitude

Guía de práctica clínica basada en la evidencia para la prevención, diagnóstico, tratamiento y seguimiento de la Enfermedad Pulmonar Obstructiva Crónica (EPOC) en población adulta

El proceso de desarrollo de la guía se describe detalladamente en el manual para desarrollar Guías de Práctica Clínica (disponible en la página web del Ministerio de Salud y Protección Social). Dicho manual se generó en un proceso con dos componentes fundamentales: uno técnico, basado en el análisis de la mejor evidencia disponible en el tema, y uno participativo en el que múltiples grupos de expertos y organizaciones interesadas hicieron su aporte en la generación del manual.Guía de práctica clínica1-63

TLR7 activation in M-CSF-dependent monocyte-derived human macrophages potentiates inflammatory responses and prompts neutrophil recruitment

Toll-like receptor 7 (TLR7) is an endosomal Pathogen-Associated Molecular Pattern (PAMP) receptor that senses single-stranded RNA (ssRNA) and whose engagement results in the production of type I IFN and pro-inflammatory cytokines upon viral exposure. Recent genetic studies have established that a dysfunctional TLR7-initiated signaling is directly linked to the development of inflammatory responses. We present evidences that TLR7 is preferentially expressed by monocyte-derived macrophages generated in the presence of M-CSF (M-MØ). We now show that TLR7 activation in M-MØ triggers a weak MAPK, NFκB and STAT1 activation and results in low production of type I IFN. Of note, TLR7 engagement re-programs MAFB+ M-MØ towards a pro-inflammatory transcriptional profile characterized by the expression of neutrophil-attracting chemokines (CXCL1-3, CXCL5, CXCL8), whose expression is dependent on the transcription factors MAFB and AhR. Moreover, TLR7-activated M-MØ display enhanced pro-inflammatory responses and a stronger production of neutrophil-attracting chemokines upon secondary stimulation. As aberrant TLR7 signaling and enhanced pulmonary neutrophil/lymphocyte ratio associate with impaired resolution of virus-induced inflammatory responses, these results suggest that targeting macrophage TLR7 might be a therapeutic strategy for viral infections where monocyte-derived macrophages exhibit a pathogenic role

Recommendations for the reactivation of laboratories of lung function tests during the pandemic by SARS-CoV-2 (COVID-19) in Colombia

La pandemia de COVID-19 plantea retos y desafíos para la salud pública y para la provisión de servicios de salud en el mundo, y Colombia no es la excepción. Con la evidencia disponible hasta el momento, se sabe que el mecanismo de transmisión más probable del SARS-CoV-2 es a distancia por gotas respiratorias mayores de 5 micras (gotas de Flügge), que no permanecen suspendidas en el aire y que se depositan en las superficies a menos de 2 metros, por contacto de las secreciones infectadas directamente con las mucosas (oral, nasal, conjuntiva) o indirectamente (a través de las manos contaminadas). No se excluye la trasmisión por aerosoles, partículas de diámetro menor de 5 micras, generadas por la tos y por procedimientos invasivos, como la toma de muestras, intubación o broncoscopia, y durante las maniobras para las pruebas de función pulmonar (PFP), razón por la cual, estas representan un alto riesgo de contagio en los laboratorios de función pulmonar. Ante este escenario se deben optar por medidas preventivas, para lo cual es necesario hacer las mejores recomendaciones, que eviten el contagio durante las pruebas, adoptando precauciones de seguridad adicionales a las ya existentes, durante y después de su realización, que inevitablemente conducirán a tiempos más largos de espera y mayor duración de las pruebas, incremento en la utilización de insumos desechables, menor flujo de pacientes y aumento de los costos. Para la reactivación de los laboratorios de función pulmonar se deben tener en cuenta la etapa de la pandemia, la urgencia del procedimiento, según el estado clínico y diagnóstico del paciente, y el tipo de prueba (Tabla 1 y 2).https://orcid.org/0000-0001-6461-2725https://orcid.org/0000-0002-3061-5212https://orcid.org/0000-0002-0100-1940https://orcid.org/0000-0002-6925-3570Revista Nacional - IndexadaN

II Colombian Tromboemblism Venous Consensus

En el trombembolismo venoso (TEV), incluye la trombosis venosa profunda (TVP) y la embolia pulmonar (EP), como manifestaciones de una misma enfermedad. Constituye un fenómeno común con una incidencia de 300-600.000 casos de TVP y cerca de 50.000 muertes anuales causadas por EP, en Estados Unidos, y 10.000 muertes anuales, por la misma razón, en Francia.171-18