Mycobacterium leprae-induced Insulin-like Growth Factor I attenuates antimicrobial mechanisms, promoting bacterial survival in macrophages.

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TitleMycobacterium leprae-induced Insulin-like Growth Factor I attenuates antimicrobial mechanisms, promoting bacterial survival in macrophages.
Publication TypeJournal Article
AuthorsBatista-Silva LR, Rodrigues LS, de Vivarini AC, da Costa FMR, de Mattos KA, Costa MRSN, Rosa PS, Toledo-Pinto TG, Dias AA, Moura DF, Sarno EN, Lopes UG, Pessolani MCV
Abbrev. JournalSci Rep
JournalScientific reports
Year of Publication2016
Volume6
Pagination27632
Publication Languageeng
Abstract

Mycobacterium leprae (ML), the etiologic agent of leprosy, can subvert macrophage antimicrobial activity by mechanisms that remain only partially understood. In the present study, the participation of hormone insulin-like growth factor I (IGF-I) in this phenomenum was investigated. Macrophages from the dermal lesions of the disseminated multibacillary lepromatous form (LL) of leprosy expressed higher levels of IGF-I than those from the self-limited paucibacillary tuberculoid form (BT). Higher levels of IGF-I secretion by ML-infected macrophages were confirmed in ex vivo and in vitro studies. Of note, the dampening of IGF-I signaling reverted the capacity of ML-infected human and murine macrophages to produce antimicrobial molecules and promoted bacterial killing. Moreover, IGF-I was shown to inhibit the JAK/STAT1-dependent signaling pathways triggered by both mycobacteria and IFN-γ most probably through its capacity to induce the suppressor of cytokine signaling-3 (SOCS3). Finally, these in vitro findings were corroborated by in vivo observations in which higher SOCS3 expression and lower phosphorylation of STAT1 levels were found in LL versus BT dermal lesions. Altogether, our data strongly suggest that IGF-I contributes to the maintenance of a functional program in infected macrophages that suits ML persistence in the host, reinforcing a key role for IGF-I in leprosy pathogenesis.

PubMed URL

http://www.ncbi.nlm.nih.gov/pubmed/27282338?dopt=Abstract

DOI10.1038/srep27632
Link to full texthttp://www.nature.com/articles/srep27632#auth-13