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This dissertation by Clara Braian explores the innate immune responses to Mycobacterium tuberculosis, the bacterium responsible for tuberculosis (TB). It examines how innate immune cells, such as macrophages and neutrophils, respond to TB infection and how they can limit bacterial growth through mechanisms like extracellular trap formation and trained immunity. The work highlights the role of extracellular traps in capturing the bacteria and the influence of β-glucans in enhancing the immune response. The research utilizes both in vitro models and advanced tissue models to study the interactions between immune cells and the pathogen. The goal is to improve understanding of the immune response to TB and to inform potential new treatments. The intended audience includes medical researchers and healthcare professionals interested in infectious diseases and immunology.

Mycobacterium tuberculosis. --- Immune response.

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

Medicine --- Immunology --- leprosy --- Mycobacterium leprae --- skin Immunity --- clinical immunopathology --- innate immunity --- adaptive immunity --- cytokine mediators --- hormonal effects --- metabolomics --- genetics --- vaccines

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Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis (MTB) and it represents a persistent public health threat for a number of complex biological and sociological reasons. According to the most recent Global Tuberculosis Report (2019) edited by the World Health Organization (WHO), TB is considered the ninth cause of death worldwide and the leading cause of mortality by a single infectious agent, with the highest rate of infections and death toll rate mostly concentrated in developing and low-income countries. We present here the editorial section to the Special Issue entitled “Mycobacterium tuberculosis Pathogenesis, Infection Prevention and Treatment” that includes 7 research articles and a review. The scientific contributions included in the Special Issue mainly focus on the characterization of MTB strains emerging in TB endemic countries as well as on multiple mechanisms adopted by the bacteria to resist and to adapt to antitubercular therapies.

Mycobacterium tuberculosis --- line probe assay --- second-line drugs --- drug resistance --- XDR-TB --- MDR-TB --- omics analysis --- TB treatment --- system analysis --- Beijing B0/W148 --- Mycobacterium smegmatis --- imidazo[1,2-b][1,2,4,5]tetrazine --- MmpS5-MmpL5 --- efflux --- drug discovery --- tuberculosis --- immune activation --- HLA-DR --- CD38 --- treatment response --- Mycobacterium --- macrophage --- apoptosis --- effector --- cytokine --- microRNA --- Beijing genotype --- Central Asia Outbreak --- murine infection model --- Virulence --- pre-XDR-TB --- Mycobacterium avium --- unique metabolic pathways --- subtractive genomics --- drug target --- uncharacterized proteins --- BM-MSCs --- Mtb --- bone-homing --- stem cell niche --- latent tuberculosis --- relapse --- liposomes --- M. tuberculosis --- host-pathogen interactions --- immune response --- antitubercular drug discovery --- antitubercular treatments --- IL-18 --- IL-18BP --- IL-18R --- gene expression

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The diagnosis of tuberculosis in the childhood population represents a major obstacle to the health system because the pediatric patient is paucibacillary. This is done by four classic criteria: epidemiological, tuberculinic, radiological and clinical; however, this method has an approximate sensitivity of 50%. On the other hand, molecular tests are new methods for the diagnosis and treatment of these infections, due to the rapidity of the result, high sensitivity, specificity and also, it reports resistance to antituberculosis drugs. Therefore, the objective of the review is to investigate the diagnosis of molecular methods in pediatric tuberculosis, since it is considered a vulnerable population, with more probability of disease progression, diagnostic problems due to the condition of being pediatric patients, the difficult microbiological isolation and therapeutic difficulties. Objective: describe the evidence on the use of molecular tests in the diagnosis of childhood tuberculosis in Latin American countries reported in the scientific literature. Materials and methods: a narrative review of the literature was performed. The selection criteria were articles that evaluated molecular tests in pediatric patients up to 18 years with a diagnosis of tuberculosis in Latin American countries. A structured search was conducted in Medline via OVID and Embase using the keywords “tuberculosis”, “pediatric”, “children”, “diagnosis” and “molecular”. The language was limited to English and Spanish, but there was no date limit. Results: 1050 articles were found, of which 751 articles were removed by the selection criteria in the title / summary and 95 articles in the full text. A qualitative analysis was performed with the 8 selected articles, which were published between 2003 and 2018, in addition 50 % of the articles were made in Peru. It was also found that the nested PCR test was implemented in 87.5 % of the studies and only 12.5 % used the GeneXpert MTB / RIF test. Most of the articles showed that nPCR has high specificity, but low sensitivity compared to liquid cultures. The nPCR has a tendency to have more false positives. Conclusions: although there are multiple molecular tests, only the report of the nested PCR test and GeneXpert MTB / RIF was found in the articles. There is little literature reported on the application of molecular diagnostic methods in the pediatric population for Latin America. El diagnóstico de tuberculosis en la población infantil representa un gran obstáculo para el sistema de salud porque el paciente pediátrico es paucibacilar. Este se realiza mediante cuatro criterios clásicos: epidemiológico, tuberculínico, radiológico y clínico; sin embargo, este método tiene una sensibilidad aproximada del 50 %. Por otro lado, las pruebas moleculares son métodos nuevos para el diagnóstico de estas infecciones, por la rapidez del resultado, una alta sensibilidad, especificidad y además, reporta la resistencia a los fármacos antituberculosos. Por lo anterior el objetivo de la revisión es investigar acerca del diagnóstico de métodos moleculares en tuberculosis pediátrica, ya que se considera que esta es una población vulnerable, teniendo más probabilidad de progresión de la enfermedad, problemas en el diagnóstico por la dificultad en la toma de los exámenes, la dificultad del aislamiento microbiológico y las dificultades terapéuticas. Objetivo: describir la evidencia sobre el uso de pruebas moleculares en el diagnóstico de tuberculosis infantil en países de Latinoamérica reportadas en la literatura científica. Materiales y métodos: se realizó una revisión narrativa de la literatura. Los criterios de selección fueron artículos que evaluaran pruebas moleculares en pacientes pediátricos hasta los 18 años con diagnóstico de tuberculosis en países de Latinoamérica. Se realizó una búsqueda estructurada en Medline vía OVID y Embase utilizando las palabras clave “tuberculosis”, “pediatric”, “children”, “diagnosis” y “molecular”. Se limitó el lenguaje al inglés y español, pero no se tuvo límite de fecha. Resultados: se encontraron 1050 artículos, de los cuales se eliminaron 751 artículos por los criterios de selección en el título/resumen y 95 artículos en el texto completo. Se realizó un análisis cualitativo con los ocho artículos seleccionados, los cuales fueron publicados entre el 2003 y 2018; además el 50 % de los artículos se realizaron en Perú. También se encontró que en el 87.5 % de los estudios se implementó la prueba PCR anidada y solo el 12.5 % utilizó la prueba GeneXpert MTB/RIF. La mayor parte de los artículos mostraron que la PCR anidada tiene alta especificidad, pero baja sensibilidad comparada con los cultivos líquidos. La nPCR tiene tendencia a tener más falsos positivos. Conclusiones: aunque existen múltiples pruebas moleculares, en los artículos solo se encontró el reporte de la prueba PCR anidada y GeneXpert MTB/RIF. Existe poca literatura reportada de la aplicación de los métodos diagnósticos moleculares en población pediátrica para Latinoamérica.

Tuberculosis --- Respiratory organs --- Research --- Diseases --- Air passages (Anatomy) --- Respiratory system --- Cardiopulmonary system --- Consumption (Disease) --- Lungs --- Phthisis --- Pulmonary tuberculosis --- TB (Disease) --- Chest --- Mycobacterial diseases --- Mycobacterium tuberculosis --- Niños --- Diagnóstico molecular --- Pulmonar --- Latinoamérica

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TB is considered as one of the oldest documented infectious diseases in the world and is believed to be the leading cause of mortality due to a single infectious agent. Mtb, the causative agent responsible for TB, continues to afflict millions of people worldwide. Furthermore, one-third of the entire world's population has latent TB. Consequently, there has been a worldwide effort to eradicate and limit the spread of Mtb through the use of antibiotics. However, management of TB is becoming more challenging with the emergence of drug-resistant and multi-drug resistant strains of Mtb. Furthermore, when administered, many of the anti-TB drugs commonly present severe complications and side effects. Novel approaches to enhance the host immune responses to completely eradicate Mtb infection are urgently needed. This Special Issue will therefore cover most recent advances in the area of host-directed therapies for TB.

Research & information: general --- Biology, life sciences --- Mycobacterium tuberculosis --- host-directed therapies --- immune responses --- tuberculosis --- lung cancer --- misdiagnosis --- invasive procedure --- revising --- antiplatelet --- aspirin --- immunomodulation --- survival --- Taiwan --- latent infection --- pulmonary --- rabbit --- iron supplementation --- pathology --- immune response --- gene expression --- Perls’ stain --- autophagy --- M. tb --- BCG vaccination --- immune exhaustion --- glutathione --- cytokines --- granulomas --- type 2 diabetes --- co-morbidities --- co-infections --- inflammation --- redox imbalance --- antioxidants --- Mycobacterium tuberculosis --- host-directed therapies --- immune responses --- tuberculosis --- lung cancer --- misdiagnosis --- invasive procedure --- revising --- antiplatelet --- aspirin --- immunomodulation --- survival --- Taiwan --- latent infection --- pulmonary --- rabbit --- iron supplementation --- pathology --- immune response --- gene expression --- Perls’ stain --- autophagy --- M. tb --- BCG vaccination --- immune exhaustion --- glutathione --- cytokines --- granulomas --- type 2 diabetes --- co-morbidities --- co-infections --- inflammation --- redox imbalance --- antioxidants