EsxA mainly contributes to the miR-155 overexpression in human monocyte-derived macrophages and potentially affect the immune mechanism of macrophages through miRNA dysregulation
Abstracts: Background/purpose: Mycobacterium tuberculosis is a successful intracellular pathogen that uses multiple proteins to survive within macrophages, one of the most remarkable is the virulence factor EsxA. In this study, we evaluate the participation of EsxA in the miRNAs expression profile...
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doaj-ca31171c200445088db9def9cc1491d82021-04-24T05:56:29ZengElsevierJournal of Microbiology, Immunology and Infection1684-11822021-04-01542185192EsxA mainly contributes to the miR-155 overexpression in human monocyte-derived macrophages and potentially affect the immune mechanism of macrophages through miRNA dysregulationMyrna Guadalupe Bonilla-Muro0Olga Nohemí Hernández de la Cruz1Juan Antonio Gonzalez-Barrios2Sofía Lizeth Alcaráz-Estrada3Mauricio Castañón-Arreola4Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Mexico City, MexicoPosgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Mexico City, MexicoCoordinación de Capacitación, Desarrollo e Investigación, Hospital Regional 1º de Octubre, ISSSTE, Mexico City, MexicoUnidad de Medicina Genómica, Centro Médico Nacional 20 de Noviembre, ISSSTE, Mexico City, MexicoPosgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Mexico City, Mexico; Corresponding author. Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, San Lorenzo 290, Colonia Del Valle Sur, Delegación Benito Juárez, CP 03100, Mexico City, Mexico.Abstracts: Background/purpose: Mycobacterium tuberculosis is a successful intracellular pathogen that uses multiple proteins to survive within macrophages, one of the most remarkable is the virulence factor EsxA. In this study, we evaluate the participation of EsxA in the miRNAs expression profile of human monocyte-derived macrophages (hMDM), to mapping out the contribution of this virulence factor in the miRNA profile and how these changes can influence and alter immune-related processes and pathways. Methods: The cytotoxic effect of rEsxA on hMDM was evaluated by the neutral red assay. The evaluation of miRNA expression profile in infected and rEsxA-stimulated hMDM was done using TaqMan Low Density Assays, and in silico analyses was carried on to construct Protein–Protein Interaction network of miRNAs targets. Results: miR-155 was the only miRNA upregulated consistently in hMDM infected with M. tuberculosis H37Rv or stimulated with rEsxA. In hMDM stimulated with rEsxA, we found 25 miRNA's dysregulated (8 up-regulated and 17 down-regulated). The most significant were the miR-155 and miR-622 that has been observed in the analysis carried out with two different endogenous controls (U6 snRNA and RNU44) for the normalization of expression analysis. This result suggests that rEsxA induces the deregulation of miRNAs that potentially target genes in key pathways for the infection control, like the MAPK signaling pathway, cytokines, and chemokine signaling pathways, and several connected pathways involved in mycobacterial uptake, vesicular traffic, and endosome maturation. Conclusion: Higher expression levels of miR-155 suggest potential roles of these miRNA in EsxA-dependent immune subversion.http://www.sciencedirect.com/science/article/pii/S1684118218300859EsxAMacrophagesmiRNAPPITuberculosisVirulence |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Myrna Guadalupe Bonilla-Muro Olga Nohemí Hernández de la Cruz Juan Antonio Gonzalez-Barrios Sofía Lizeth Alcaráz-Estrada Mauricio Castañón-Arreola |
spellingShingle |
Myrna Guadalupe Bonilla-Muro Olga Nohemí Hernández de la Cruz Juan Antonio Gonzalez-Barrios Sofía Lizeth Alcaráz-Estrada Mauricio Castañón-Arreola EsxA mainly contributes to the miR-155 overexpression in human monocyte-derived macrophages and potentially affect the immune mechanism of macrophages through miRNA dysregulation Journal of Microbiology, Immunology and Infection EsxA Macrophages miRNA PPI Tuberculosis Virulence |
author_facet |
Myrna Guadalupe Bonilla-Muro Olga Nohemí Hernández de la Cruz Juan Antonio Gonzalez-Barrios Sofía Lizeth Alcaráz-Estrada Mauricio Castañón-Arreola |
author_sort |
Myrna Guadalupe Bonilla-Muro |
title |
EsxA mainly contributes to the miR-155 overexpression in human monocyte-derived macrophages and potentially affect the immune mechanism of macrophages through miRNA dysregulation |
title_short |
EsxA mainly contributes to the miR-155 overexpression in human monocyte-derived macrophages and potentially affect the immune mechanism of macrophages through miRNA dysregulation |
title_full |
EsxA mainly contributes to the miR-155 overexpression in human monocyte-derived macrophages and potentially affect the immune mechanism of macrophages through miRNA dysregulation |
title_fullStr |
EsxA mainly contributes to the miR-155 overexpression in human monocyte-derived macrophages and potentially affect the immune mechanism of macrophages through miRNA dysregulation |
title_full_unstemmed |
EsxA mainly contributes to the miR-155 overexpression in human monocyte-derived macrophages and potentially affect the immune mechanism of macrophages through miRNA dysregulation |
title_sort |
esxa mainly contributes to the mir-155 overexpression in human monocyte-derived macrophages and potentially affect the immune mechanism of macrophages through mirna dysregulation |
publisher |
Elsevier |
series |
Journal of Microbiology, Immunology and Infection |
issn |
1684-1182 |
publishDate |
2021-04-01 |
description |
Abstracts: Background/purpose: Mycobacterium tuberculosis is a successful intracellular pathogen that uses multiple proteins to survive within macrophages, one of the most remarkable is the virulence factor EsxA. In this study, we evaluate the participation of EsxA in the miRNAs expression profile of human monocyte-derived macrophages (hMDM), to mapping out the contribution of this virulence factor in the miRNA profile and how these changes can influence and alter immune-related processes and pathways. Methods: The cytotoxic effect of rEsxA on hMDM was evaluated by the neutral red assay. The evaluation of miRNA expression profile in infected and rEsxA-stimulated hMDM was done using TaqMan Low Density Assays, and in silico analyses was carried on to construct Protein–Protein Interaction network of miRNAs targets. Results: miR-155 was the only miRNA upregulated consistently in hMDM infected with M. tuberculosis H37Rv or stimulated with rEsxA. In hMDM stimulated with rEsxA, we found 25 miRNA's dysregulated (8 up-regulated and 17 down-regulated). The most significant were the miR-155 and miR-622 that has been observed in the analysis carried out with two different endogenous controls (U6 snRNA and RNU44) for the normalization of expression analysis. This result suggests that rEsxA induces the deregulation of miRNAs that potentially target genes in key pathways for the infection control, like the MAPK signaling pathway, cytokines, and chemokine signaling pathways, and several connected pathways involved in mycobacterial uptake, vesicular traffic, and endosome maturation. Conclusion: Higher expression levels of miR-155 suggest potential roles of these miRNA in EsxA-dependent immune subversion. |
topic |
EsxA Macrophages miRNA PPI Tuberculosis Virulence |
url |
http://www.sciencedirect.com/science/article/pii/S1684118218300859 |
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