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Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):12833-8. doi: 10.1073/pnas.1016496108. Epub 2011 Jul 18.

Mycolactone impairs T cell homing by suppressing microRNA control of L-selectin expression.

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1
Institut Pasteur, Unité de Pathogénomique Mycobactérienne Intégrée, 75015 Paris, France.

Abstract

Mycolactone is a macrolide produced by Mycobacterium ulcerans with immunomodulatory properties. Here, we describe that in mouse, mycolactone injection led to a massive T-cell depletion in peripheral lymph nodes (PLNs) that was associated with defective expression of L-selectin (CD62-L). Importantly, preexposure to mycolactone impaired the capacity of T cells to reach PLNs after adoptive transfer, respond to chemotactic signals, and expand upon antigenic stimulation in vivo. We found that mycolactone-induced suppression of CD62-L expression by human primary T cells was induced rapidly at both the mRNA and protein levels and correlated with the reduced expression of one miRNA: let-7b. Notably, silencing of let-7b was sufficient to inhibit CD62-L gene expression. Conversely, its overexpression tended to up-regulate CD62-L and counteract the effects of mycolactone. Our results identify T-cell homing as a biological process targeted by mycolactone. Moreover, they reveal a mechanism of control of CD62-L expression involving the miRNA let-7b.

PMID:
21768364
PMCID:
PMC3150933
DOI:
10.1073/pnas.1016496108
[Indexed for MEDLINE]
Free PMC Article
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