Universität zu Köln

Schnitger, Anna K. D., Machova, Alzbeta, Mueller, Roman Ulrich, Androulidaki, Ariadne, Schermer, Bernhard ORCID: 0000-0002-5194-9000, Pasparakis, Manolis ORCID: 0000-0002-9870-0966, Kroenke, Martin and Papadopoulou, Nikoletta (2011). Listeria monocytogenes Infection in Macrophages Induces Vacuolar-Dependent Host miRNA Response. PLoS One, 6 (11). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

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 Delta hly, 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-kappa B 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schnitger, Anna K. D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Machova, Alzbeta UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Roman Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Androulidaki, Ariadne UNSPECIFIED UNSPECIFIED UNSPECIFIED Schermer, Bernhard UNSPECIFIED orcid.org/0000-0002-5194-9000 UNSPECIFIED Pasparakis, Manolis UNSPECIFIED orcid.org/0000-0002-9870-0966 UNSPECIFIED Kroenke, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Papadopoulou, Nikoletta UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-485323
DOI:	10.1371/journal.pone.0027435
Journal or Publication Title:	PLoS One
Volume:	6
Number:	11
Date:	2011
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TRANSCRIPTION FACTORS; IMMUNE-RESPONSES; MICRORNA; INNATE; EXPRESSION; INDUCTION; MIR-155; STIMULATION; RECOGNITION; REGULATORS Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48532