02162nas a2200277   4500000000100000008004100001100002200042700001700064700001600081700001400097700001400111700001500125700001100140700002100151700001200172700001300184700001200197700001200209700001600221245014400237856005300381300001000434490000600444520142000450022001401870       2016                            d1 aBatista-Silva L R1 aRodrigues LS1 aVivarini AC1 aCosta FMR1 aMattos KA1 aCosta MRSN1 aRosa P1 aToledo-Pinto T G1 aDias AA1 aMoura DF1 aSarno E1 aLopes U1 aPessolani M00aMycobacterium leprae-induced Insulin-like Growth Factor I attenuates antimicrobial mechanisms, promoting bacterial survival in macrophages.  uhttp://www.nature.com/articles/srep27632#auth-13  a276320 v63 a<p>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.</p>
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