A new paradigm for leprosy diagnosis based on host gene expression
| العنوان: | A new paradigm for leprosy diagnosis based on host gene expression |
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| المؤلفون: | Euzenir Nunes Sarno, Andrej Benjak, Stewart T. Cole, Philippe Busso, Charlotte Avanzi, Thyago Leal-Calvo, Milton Ozório Moraes, Roberta Olmo Pinheiro, Mayara Abud Mendes |
| المصدر: | PLoS Pathogens, Vol 17, Iss 10 (2021) PLoS Pathogens PLoS Pathogens, Vol 17, Iss 10, p e1009972 (2021) |
| بيانات النشر: | Public Library of Science (PLoS), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Bacterial Diseases, Keratinocytes, Molecular biology, Microarrays, Gene Expression, Disease, regularization paths, Epithelium, Transcriptome, 0302 clinical medicine, Medical Conditions, Sequencing techniques, Animal Cells, Medicine and Health Sciences, Biology (General), Mycobacterium leprae, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), cell-like cells, 0303 health sciences, biology, RNA sequencing, microarray data, Mycobacterium Leprae, 3. Good health, Actinobacteria, Infectious Diseases, Bioassays and Physiological Analysis, rna-seq, 030220 oncology & carcinogenesis, Leprosy, Cellular Types, Anatomy, powerful, TLR10, Research Article, Neglected Tropical Diseases, Genetic Markers, GeneralLiterature_INTRODUCTORYANDSURVEY, QH301-705.5, Immunology, emt, Microbiology, 03 medical and health sciences, mycobacterium-leprae, Immune system, Signs and Symptoms, Diagnostic Medicine, Virology, medicine, Genetics, Humans, cancer, RNA, Messenger, Granuloma annulare, 030304 developmental biology, Bacteria, Microarray analysis techniques, Gene Expression Profiling, Organisms, Biology and Life Sciences, Epithelial Cells, Cell Biology, RC581-607, medicine.disease, biology.organism_classification, Tropical Diseases, quantification, Research and analysis methods, Molecular biology techniques, Biological Tissue, 2,3-dioxygenase, Lesions, Parasitology, Clinical Medicine, Immunologic diseases. Allergy |
| الوصف: | Author summary Despite effective treatment, leprosy is still a significant public health issue in more than 120 countries, with more than 200 000 new cases yearly. The disease is caused mainly by Mycobacterium leprae, a slow-growing bacillus still uncultivable in axenic media. This limitation has hampered basic research into host-pathogen interaction and the development of new diagnostic assays. Currently, leprosy is diagnosed clinically, with no standalone diagnostic assay accurate enough for all clinical forms. Here, we use RNA-seq transcriptome profiling in leprosy lesions and granuloma annulare to identify mRNA biomarkers with potential diagnostic applications. Also, we explored new pathways that can be useful in further understanding the host-pathogen interaction and how the bacteria bypass host immune defenses. We found that IDO1, a gene involved with tryptophan catabolism, is an excellent candidate for distinguishing leprosy lesions from other dermatoses. Additionally, we observed that a previous signature of keratinocyte development and cornification negatively correlates with epithelial-mesenchymal transition genes in the skin, suggesting new ways in which the pathogen may subvert its host to survive and spread throughout the body. Our study identifies new mRNA biomarkers that can improve leprosy diagnostics and describe new insights about host-pathogen interactions in human skin. Transcriptional profiling is a powerful tool to investigate and detect human diseases. In this study, we used bulk RNA-sequencing (RNA-Seq) to compare the transcriptomes in skin lesions of leprosy patients or controls affected by other dermal conditions such as granuloma annulare, a confounder for paucibacillary leprosy. We identified five genes capable of accurately distinguishing multibacillary and paucibacillary leprosy from other skin conditions. Indoleamine 2,3-dioxygenase 1 (IDO1) expression alone was highly discriminatory, followed by TLR10, BLK, CD38, and SLAMF7, whereas the HS3ST2 and CD40LG mRNA separated multi- and paucibacillary leprosy. Finally, from the main differentially expressed genes (DEG) and enriched pathways, we conclude that paucibacillary disease is characterized by epithelioid transformation and granuloma formation, with an exacerbated cellular immune response, while multibacillary leprosy features epithelial-mesenchymal transition with phagocytic and lipid biogenesis patterns in the skin. These findings will help catalyze the development of better diagnostic tools and potential host-based therapeutic interventions. Finally, our data may help elucidate host-pathogen interplay driving disease clinical manifestations. |
| اللغة: | English |
| تدمد: | 1553-7374 1553-7366 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::420afd6bc8989b879d17d1aebd571e12Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568100/?tool=EBITest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....420afd6bc8989b879d17d1aebd571e12 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537374 15537366 |
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