Listeria monocytogenes infection in macrophages induces vacuolar-dependent host miRNA response.

Listeria monocytogenes is a gram-positive facultative intracellular pathogen, causing serious illness in immunocompromised individuals and pregnant women. Upon detection by macrophages, which are key players of the innate immune response against infection, L. monocytogenes induces specific host cell...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Anna K D Schnitger, Alzbeta Machova, Roman Ulrich Mueller, Ariadne Androulidaki, Bernhard Schermer, Manolis Pasparakis, Martin Krönke, Nikoletta Papadopoulou
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2011
Materias:
R
Q
Acceso en línea:https://doaj.org/article/65d64410a33f4008824ed4a4eba7edd8
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:65d64410a33f4008824ed4a4eba7edd8
record_format dspace
spelling oai:doaj.org-article:65d64410a33f4008824ed4a4eba7edd82021-11-18T07:34:01ZListeria monocytogenes infection in macrophages induces vacuolar-dependent host miRNA response.1932-620310.1371/journal.pone.0027435https://doaj.org/article/65d64410a33f4008824ed4a4eba7edd82011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22114673/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Listeria monocytogenes is a gram-positive facultative intracellular pathogen, causing serious illness in immunocompromised individuals and pregnant women. Upon detection by macrophages, which are key players of the innate immune response against infection, L. monocytogenes induces specific host cell responses which need to be tightly controlled at transcriptional and post-transcriptional levels. Here, we ask whether and how host miRNAs, which represent an important mechanism of post-transcriptional regulation in a wide array of biological processes, are altered by a model pathogen upon live infection of murine bone marrow derived macrophages. We first report that L. monocytogenes subverts the host genome-wide miRNA profile of macrophages in vitro. Specifically, we show that miR-155, miR-146a, miR-125a-3p/5p and miR-149 were amongst the most significantly regulated miRNAs in infected macrophages. Strikingly, these miRNAs were highly upregulated upon infection with the Listeriolysin-deficient L. monocytogenes mutant Δhly, that cannot escape from the phagosome thus representing a vacuolar-contained infection. The vacuolar miRNA response was significantly reduced in macrophages deficient for MyD88. In addition, miR-146a and miR-125a-3p/5p were regulated at transcriptional levels upon infection, and miR-125a-3p/5p were found to be TLR2 responsive. Furthermore, miR-155 transactivation in infection was regulated by NF-κB p65, while miR-146a and miR-125a-3p/5p expression was unaffected in p65-deficient primary macrophages upon L. monocytogenes infection. Our results demonstrate that L. monocytogenes promotes significant changes in the miRNA expression profile in macrophages, and reveal a vacuolar-dependent miRNA signature, listeriolysin-independent and MyD88-dependent. These miRNAs are predicted to target immune genes and are therefore most likely involved in regulation of the macrophage innate immune response against infection at post-transcriptional levels.Anna K D SchnitgerAlzbeta MachovaRoman Ulrich MuellerAriadne AndroulidakiBernhard SchermerManolis PasparakisMartin KrönkeNikoletta PapadopoulouPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e27435 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Anna K D Schnitger
Alzbeta Machova
Roman Ulrich Mueller
Ariadne Androulidaki
Bernhard Schermer
Manolis Pasparakis
Martin Krönke
Nikoletta Papadopoulou
Listeria monocytogenes infection in macrophages induces vacuolar-dependent host miRNA response.
description Listeria monocytogenes is a gram-positive facultative intracellular pathogen, causing serious illness in immunocompromised individuals and pregnant women. Upon detection by macrophages, which are key players of the innate immune response against infection, L. monocytogenes induces specific host cell responses which need to be tightly controlled at transcriptional and post-transcriptional levels. Here, we ask whether and how host miRNAs, which represent an important mechanism of post-transcriptional regulation in a wide array of biological processes, are altered by a model pathogen upon live infection of murine bone marrow derived macrophages. We first report that L. monocytogenes subverts the host genome-wide miRNA profile of macrophages in vitro. Specifically, we show that miR-155, miR-146a, miR-125a-3p/5p and miR-149 were amongst the most significantly regulated miRNAs in infected macrophages. Strikingly, these miRNAs were highly upregulated upon infection with the Listeriolysin-deficient L. monocytogenes mutant Δhly, that cannot escape from the phagosome thus representing a vacuolar-contained infection. The vacuolar miRNA response was significantly reduced in macrophages deficient for MyD88. In addition, miR-146a and miR-125a-3p/5p were regulated at transcriptional levels upon infection, and miR-125a-3p/5p were found to be TLR2 responsive. Furthermore, miR-155 transactivation in infection was regulated by NF-κB p65, while miR-146a and miR-125a-3p/5p expression was unaffected in p65-deficient primary macrophages upon L. monocytogenes infection. Our results demonstrate that L. monocytogenes promotes significant changes in the miRNA expression profile in macrophages, and reveal a vacuolar-dependent miRNA signature, listeriolysin-independent and MyD88-dependent. These miRNAs are predicted to target immune genes and are therefore most likely involved in regulation of the macrophage innate immune response against infection at post-transcriptional levels.
format article
author Anna K D Schnitger
Alzbeta Machova
Roman Ulrich Mueller
Ariadne Androulidaki
Bernhard Schermer
Manolis Pasparakis
Martin Krönke
Nikoletta Papadopoulou
author_facet Anna K D Schnitger
Alzbeta Machova
Roman Ulrich Mueller
Ariadne Androulidaki
Bernhard Schermer
Manolis Pasparakis
Martin Krönke
Nikoletta Papadopoulou
author_sort Anna K D Schnitger
title Listeria monocytogenes infection in macrophages induces vacuolar-dependent host miRNA response.
title_short Listeria monocytogenes infection in macrophages induces vacuolar-dependent host miRNA response.
title_full Listeria monocytogenes infection in macrophages induces vacuolar-dependent host miRNA response.
title_fullStr Listeria monocytogenes infection in macrophages induces vacuolar-dependent host miRNA response.
title_full_unstemmed Listeria monocytogenes infection in macrophages induces vacuolar-dependent host miRNA response.
title_sort listeria monocytogenes infection in macrophages induces vacuolar-dependent host mirna response.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/65d64410a33f4008824ed4a4eba7edd8
work_keys_str_mv AT annakdschnitger listeriamonocytogenesinfectioninmacrophagesinducesvacuolardependenthostmirnaresponse
AT alzbetamachova listeriamonocytogenesinfectioninmacrophagesinducesvacuolardependenthostmirnaresponse
AT romanulrichmueller listeriamonocytogenesinfectioninmacrophagesinducesvacuolardependenthostmirnaresponse
AT ariadneandroulidaki listeriamonocytogenesinfectioninmacrophagesinducesvacuolardependenthostmirnaresponse
AT bernhardschermer listeriamonocytogenesinfectioninmacrophagesinducesvacuolardependenthostmirnaresponse
AT manolispasparakis listeriamonocytogenesinfectioninmacrophagesinducesvacuolardependenthostmirnaresponse
AT martinkronke listeriamonocytogenesinfectioninmacrophagesinducesvacuolardependenthostmirnaresponse
AT nikolettapapadopoulou listeriamonocytogenesinfectioninmacrophagesinducesvacuolardependenthostmirnaresponse
_version_ 1718423288318787584