Integrated microRNA-mRNA-analysis of human monocyte derived macrophages upon Mycobacterium avium subsp. hominissuis infection.

<h4>Background</h4>Many efforts have been made to understand basal mechanisms of mycobacterial infections. Macrophages are the first line of host immune defence to encounter and eradicate mycobacteria. Pathogenic species have evolved different mechanisms to evade host response, e.g. by i...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jutta Sharbati, Astrid Lewin, Barbara Kutz-Lohroff, Elisabeth Kamal, Ralf Einspanier, Soroush Sharbati
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4b6100548ce2466da5d35aeefcdff7ee
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4b6100548ce2466da5d35aeefcdff7ee
record_format	dspace
spelling	oai:doaj.org-article:4b6100548ce2466da5d35aeefcdff7ee2021-11-18T06:53:24ZIntegrated microRNA-mRNA-analysis of human monocyte derived macrophages upon Mycobacterium avium subsp. hominissuis infection.1932-620310.1371/journal.pone.0020258https://doaj.org/article/4b6100548ce2466da5d35aeefcdff7ee2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21629653/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Many efforts have been made to understand basal mechanisms of mycobacterial infections. Macrophages are the first line of host immune defence to encounter and eradicate mycobacteria. Pathogenic species have evolved different mechanisms to evade host response, e.g. by influencing macrophage apoptotic pathways. However, the underlying molecular regulation is not fully understood. A new layer of eukaryotic regulation of gene expression is constituted by microRNAs. Therefore, we present a comprehensive study for identification of these key regulators and their targets in the context of host macrophage response to mycobacterial infections.<h4>Methodology/principal findings</h4>We performed microRNA as well as mRNA expression analysis of human monocyte derived macrophages infected with several Mycobacterium avium hominissuis strains by means of microarrays as well as quantitative reverse transcription PCR (qRT-PCR). The data revealed the ability of all strains to inhibit apoptosis by transcriptional regulation of BCL2 family members. Accordingly, at 48 h after infection macrophages infected with all M. avium strains showed significantly decreased caspase 3 and 7 activities compared to the controls. Expression of let-7e, miR-29a and miR-886-5p were increased in response to mycobacterial infection at 48 h. The integrated analysis of microRNA and mRNA expression as well as target prediction pointed out regulative networks identifying caspase 3 and 7 as potential targets of let-7e and miR-29a, respectively. Consecutive reporter assays verified the regulation of caspase 3 and 7 by these microRNAs.<h4>Conclusions/significance</h4>We show for the first time that mycobacterial infection of human macrophages causes a specific microRNA response. We furthermore outlined a regulatory network of potential interactions between microRNAs and mRNAs. This study provides a theoretical concept for unveiling how distinct mycobacteria could manipulate host cell response. In addition, functional relevance was confirmed by uncovering the control of major caspases 3 and 7 by let-7e and miR-29a, respectively.Jutta SharbatiAstrid LewinBarbara Kutz-LohroffElisabeth KamalRalf EinspanierSoroush SharbatiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 5, p e20258 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jutta Sharbati Astrid Lewin Barbara Kutz-Lohroff Elisabeth Kamal Ralf Einspanier Soroush Sharbati Integrated microRNA-mRNA-analysis of human monocyte derived macrophages upon Mycobacterium avium subsp. hominissuis infection.
description	<h4>Background</h4>Many efforts have been made to understand basal mechanisms of mycobacterial infections. Macrophages are the first line of host immune defence to encounter and eradicate mycobacteria. Pathogenic species have evolved different mechanisms to evade host response, e.g. by influencing macrophage apoptotic pathways. However, the underlying molecular regulation is not fully understood. A new layer of eukaryotic regulation of gene expression is constituted by microRNAs. Therefore, we present a comprehensive study for identification of these key regulators and their targets in the context of host macrophage response to mycobacterial infections.<h4>Methodology/principal findings</h4>We performed microRNA as well as mRNA expression analysis of human monocyte derived macrophages infected with several Mycobacterium avium hominissuis strains by means of microarrays as well as quantitative reverse transcription PCR (qRT-PCR). The data revealed the ability of all strains to inhibit apoptosis by transcriptional regulation of BCL2 family members. Accordingly, at 48 h after infection macrophages infected with all M. avium strains showed significantly decreased caspase 3 and 7 activities compared to the controls. Expression of let-7e, miR-29a and miR-886-5p were increased in response to mycobacterial infection at 48 h. The integrated analysis of microRNA and mRNA expression as well as target prediction pointed out regulative networks identifying caspase 3 and 7 as potential targets of let-7e and miR-29a, respectively. Consecutive reporter assays verified the regulation of caspase 3 and 7 by these microRNAs.<h4>Conclusions/significance</h4>We show for the first time that mycobacterial infection of human macrophages causes a specific microRNA response. We furthermore outlined a regulatory network of potential interactions between microRNAs and mRNAs. This study provides a theoretical concept for unveiling how distinct mycobacteria could manipulate host cell response. In addition, functional relevance was confirmed by uncovering the control of major caspases 3 and 7 by let-7e and miR-29a, respectively.
format	article
author	Jutta Sharbati Astrid Lewin Barbara Kutz-Lohroff Elisabeth Kamal Ralf Einspanier Soroush Sharbati
author_facet	Jutta Sharbati Astrid Lewin Barbara Kutz-Lohroff Elisabeth Kamal Ralf Einspanier Soroush Sharbati
author_sort	Jutta Sharbati
title	Integrated microRNA-mRNA-analysis of human monocyte derived macrophages upon Mycobacterium avium subsp. hominissuis infection.
title_short	Integrated microRNA-mRNA-analysis of human monocyte derived macrophages upon Mycobacterium avium subsp. hominissuis infection.
title_full	Integrated microRNA-mRNA-analysis of human monocyte derived macrophages upon Mycobacterium avium subsp. hominissuis infection.
title_fullStr	Integrated microRNA-mRNA-analysis of human monocyte derived macrophages upon Mycobacterium avium subsp. hominissuis infection.
title_full_unstemmed	Integrated microRNA-mRNA-analysis of human monocyte derived macrophages upon Mycobacterium avium subsp. hominissuis infection.
title_sort	integrated microrna-mrna-analysis of human monocyte derived macrophages upon mycobacterium avium subsp. hominissuis infection.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/4b6100548ce2466da5d35aeefcdff7ee
work_keys_str_mv	AT juttasharbati integratedmicrornamrnaanalysisofhumanmonocytederivedmacrophagesuponmycobacteriumaviumsubsphominissuisinfection AT astridlewin integratedmicrornamrnaanalysisofhumanmonocytederivedmacrophagesuponmycobacteriumaviumsubsphominissuisinfection AT barbarakutzlohroff integratedmicrornamrnaanalysisofhumanmonocytederivedmacrophagesuponmycobacteriumaviumsubsphominissuisinfection AT elisabethkamal integratedmicrornamrnaanalysisofhumanmonocytederivedmacrophagesuponmycobacteriumaviumsubsphominissuisinfection AT ralfeinspanier integratedmicrornamrnaanalysisofhumanmonocytederivedmacrophagesuponmycobacteriumaviumsubsphominissuisinfection AT soroushsharbati integratedmicrornamrnaanalysisofhumanmonocytederivedmacrophagesuponmycobacteriumaviumsubsphominissuisinfection
_version_	1718424227259875328

Integrated microRNA-mRNA-analysis of human monocyte derived macrophages upon Mycobacterium avium subsp. hominissuis infection.

Ejemplares similares