title: Mycolactone impairs T cell homing by suppressing microRNA control of L-selectin expression.
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.
authors.affiliation: Institut Pasteur, Unité de Pathogénomique Mycobactérienne Intégrée, 75015 Paris, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Guenin-Macé
authors.forename: Florent
authors.initials: F
authors.lastname: Carrette
authors.forename: François
authors.initials: F
authors.lastname: Asperti-Boursin
authors.forename: Agnès
authors.initials: A
authors.lastname: Le Bon
authors.forename: Laxmee
authors.initials: L
authors.lastname: Caleechurn
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Bartolo
authors.forename: Arnaud
authors.initials: A
authors.lastname: Fontanet
authors.forename: Georges
authors.initials: G
authors.lastname: Bismuth
authors.forename: Caroline
authors.initials: C
authors.lastname: Demangel
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D019169:Jurkat Cells; D019041:L-Selectin / Q000235:genetics* / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism; D018942:Macrolides; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
chemical_list: D001427:Bacterial Toxins; D018942:Macrolides; D035683:MicroRNAs; C542687:mirnlet7 microRNA, mouse; C117218:mycolactone; D019041:L-Selectin