03104nas a2200529   4500000000100000008004100001260000900042653002000051653001500071653002100086653001100107653003000118653003100148653003100179653001100210653001200221653002100233653000900254653001700263653002400280653002500304653004400329653002200373653001800395653001800413100001800431700002500449700002000474700002000494700001700514700001100531700001600542700001400558700001500572700001400587700001200601700001600613700001600629700001300645245010900658856007700767300001100844490000600855050001900861520168000880022001402560       2013                            d  c201310aCells, Cultured10aChemokines10aCluster Analysis10aFemale10aGene Expression Profiling10aGene Expression Regulation10aHost-Pathogen Interactions10aHumans10aleprosy10aLipid Metabolism10aMale10aMitochondria10aMycobacterium bovis10aMycobacterium leprae10aOligonucleotide Array Sequence Analysis10aPeripheral nerves10aSchwann Cells10aTranscriptome1 aGuerreiro LTA1 aRobottom-Ferreira AB1 aRibeiro-Alves M1 aToledo-Pinto TG1 aRosa Brito T1 aRosa P1 aSandoval FG1 aJardim MR1 aAntunes SG1 aShannon E1 aSarno E1 aPessolani M1 aWilliams DL1 aMoraes M00aGene expression profiling specifies chemokine, mitochondrial and lipid metabolism signatures in leprosy.  uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683049/pdf/pone.0064748.pdf  ae647480 v8  aGUERREIRO 20133 a<p>Herein, we performed microarray experiments in Schwann cells infected with live M. leprae and identified novel differentially expressed genes (DEG) in M. leprae infected cells. Also, we selected candidate genes associated or implicated with leprosy in genetic studies and biological experiments. Forty-seven genes were selected for validation in two independent types of samples by multiplex qPCR. First, an in vitro model using THP-1 cells was infected with live Mycobacterium leprae and M. bovis bacillus Calmette-Guérin (BCG). In a second situation, mRNA obtained from nerve biopsies from patients with leprosy or other peripheral neuropathies was tested. We detected DEGs that discriminate M. bovis BCG from M. leprae infection. Specific signatures of susceptible responses after M. leprae infection when compared to BCG lead to repression of genes, including CCL2, CCL3, IL8 and SOD2. The same 47-gene set was screened in nerve biopsies, which corroborated the down-regulation of CCL2 and CCL3 in leprosy, but also evidenced the down-regulation of genes involved in mitochondrial metabolism, and the up-regulation of genes involved in lipid metabolism and ubiquitination. Finally, a gene expression signature from DEG was identified in patients confirmed of having leprosy. A classification tree was able to ascertain 80% of the cases as leprosy or non-leprous peripheral neuropathy based on the expression of only LDLR and CCL4. A general immune and mitochondrial hypo-responsive state occurs in response to M. leprae infection. Also, the most important genes and pathways have been highlighted providing new tools for early diagnosis and treatment of leprosy. </p>  a1932-6203