02811nas a2200385   4500000000100000008004100001260001600042653001200058653001100070653002500081653002100106653001700127653001200144653002100156653001100177653000900188653002300197653002500220653002500245653001800270653002500288100001400313700001500327700001400342700001600356700001600372700001200388700001700400700001200417245014700429300001200576490000800588520181500596022001402411       2011                            d  c2011 Sep 0110aAnimals10aHumans10aImmunohistochemistry10aInclusion Bodies10aInflammation10aleprosy10aLipid Metabolism10aLipids10aMice10aMice, Inbred C57BL10aMicroscopy, Confocal10aMycobacterium leprae10aSchwann Cells10aToll-Like Receptor 61 aMattos KA1 aOliveira V1 aD'Avila H1 aRodrigues L1 aPinheiro RO1 aSarno E1 aPessolani MC1 aBozza P00aTLR6-driven lipid droplets in Mycobacterium leprae-infected Schwann cells: immunoinflammatory platforms associated with bacterial persistence.  a2548-580 v1873 a<p>The mechanisms responsible for nerve injury in leprosy need further elucidation. We recently demonstrated that the foamy phenotype of Mycobacterium leprae-infected Schwann cells (SCs) observed in nerves of multibacillary patients results from the capacity of M. leprae to induce and recruit lipid droplets (LDs; also known as lipid bodies) to bacterial-containing phagosomes. In this study, we analyzed the parameters that govern LD biogenesis by M. leprae in SCs and how this contributes to the innate immune response elicited by M. leprae. Our observations indicated that LD formation requires the uptake of live bacteria and depends on host cell cytoskeleton rearrangement and vesicular trafficking. TLR6 deletion, but not TLR2, completely abolished the induction of LDs by M. leprae, as well as inhibited the bacterial uptake in SCs. M. leprae-induced LD biogenesis correlated with increased PGE(2) and IL-10 secretion, as well as reduced IL-12 and NO production in M. leprae-infected SCs. Analysis of nerves from lepromatous leprosy patients showed colocalization of M. leprae, LDs, and cyclooxygenase-2 in SCs, indicating that LDs are sites for PGE(2) synthesis in vivo. LD biogenesis Inhibition by the fatty acid synthase inhibitor C-75 abolished the effect of M. leprae on SC production of immunoinflammatory mediators and enhanced the mycobacterial-killing ability of SCs. Altogether, our data indicated a critical role for TLR6-dependent signaling in M. leprae-SC interactions, favoring phagocytosis and subsequent signaling for induction of LD biogenesis in infected cells. Moreover, our observations reinforced the role of LDs favoring mycobacterial survival and persistence in the nerve. These findings give further support to a critical role for LDs in M. leprae pathogenesis in the nerve.</p>  a1550-6606