A new paradigm for leprosy diagnosis based on host gene expression

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 p...

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Autores principales:	Thyago Leal-Calvo, Charlotte Avanzi, Mayara Abud Mendes, Andrej Benjak, Philippe Busso, Roberta Olmo Pinheiro, Euzenir Nunes Sarno, Stewart Thomas Cole, Milton Ozório Moraes
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ea7647be84d24cc2a8be5dccda278b62
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spelling	oai:doaj.org-article:ea7647be84d24cc2a8be5dccda278b622021-11-11T06:03:59ZA new paradigm for leprosy diagnosis based on host gene expression1553-73661553-7374https://doaj.org/article/ea7647be84d24cc2a8be5dccda278b622021-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568100/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Transcriptional 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. 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.Thyago Leal-CalvoCharlotte AvanziMayara Abud MendesAndrej BenjakPhilippe BussoRoberta Olmo PinheiroEuzenir Nunes SarnoStewart Thomas ColeMilton Ozório MoraesPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Thyago Leal-Calvo Charlotte Avanzi Mayara Abud Mendes Andrej Benjak Philippe Busso Roberta Olmo Pinheiro Euzenir Nunes Sarno Stewart Thomas Cole Milton Ozório Moraes A new paradigm for leprosy diagnosis based on host gene expression
description	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. 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.
format	article
author	Thyago Leal-Calvo Charlotte Avanzi Mayara Abud Mendes Andrej Benjak Philippe Busso Roberta Olmo Pinheiro Euzenir Nunes Sarno Stewart Thomas Cole Milton Ozório Moraes
author_facet	Thyago Leal-Calvo Charlotte Avanzi Mayara Abud Mendes Andrej Benjak Philippe Busso Roberta Olmo Pinheiro Euzenir Nunes Sarno Stewart Thomas Cole Milton Ozório Moraes
author_sort	Thyago Leal-Calvo
title	A new paradigm for leprosy diagnosis based on host gene expression
title_short	A new paradigm for leprosy diagnosis based on host gene expression
title_full	A new paradigm for leprosy diagnosis based on host gene expression
title_fullStr	A new paradigm for leprosy diagnosis based on host gene expression
title_full_unstemmed	A new paradigm for leprosy diagnosis based on host gene expression
title_sort	new paradigm for leprosy diagnosis based on host gene expression
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/ea7647be84d24cc2a8be5dccda278b62
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A new paradigm for leprosy diagnosis based on host gene expression

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