MicroRNA-21 targets the vitamin D–dependent antimicrobial pathway in leprosy View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-02

AUTHORS

Philip T Liu, Matthew Wheelwright, Rosane Teles, Evangelia Komisopoulou, Kristina Edfeldt, Benjamin Ferguson, Manali D Mehta, Aria Vazirnia, Thomas H Rea, Euzenir N Sarno, Thomas G Graeber, Robert L Modlin

ABSTRACT

Leprosy provides a model to investigate mechanisms of immune regulation in humans, given that the disease forms a spectrum of clinical presentations that correlate with host immune responses. Here we identified 13 miRNAs that were differentially expressed in the lesions of subjects with progressive lepromatous (L-lep) versus the self-limited tuberculoid (T-lep) disease. Bioinformatic analysis revealed a significant enrichment of L-lep-specific miRNAs that preferentially target key immune genes downregulated in L-lep versus T-lep lesions. The most differentially expressed miRNA in L-lep lesions, hsa-mir-21, was upregulated in Mycobacterium leprae-infected monocytes. By directly downregulating Toll-like receptor 2/1 heterodimer (TLR2/1)-induced CYP27B1 and IL1B expression as well as indirectly upregulating interleukin-10 (IL-10), hsa-mir-21 inhibited expression of the genes encoding two vitamin D-dependent antimicrobial peptides, CAMP and DEFB4A. Conversely, knockdown of hsa-mir-21 in M. leprae-infected monocytes enhanced expression of CAMP and DEFB4A and restored TLR2/1-mediated antimicrobial activity against M. leprae. Therefore, the ability of M. leprae to upregulate hsa-mir-21 targets multiple genes associated with the immunologically localized disease form, providing an effective mechanism to escape from the vitamin D-dependent antimicrobial pathway. More... »

PAGES

267

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nm.2584

DOI

http://dx.doi.org/10.1038/nm.2584

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1008635452

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22286305


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nm.2584'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nm.2584'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nm.2584'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nm.2584'


 

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