Identification of a systemic interferon- γ inducible antimicrobial gene signature in leprosy patients undergoing reversal reaction

by Rosane M. B. Teles, Jing Lu, Maria Ti ó-Coma, Isabela M. B. Goulart, Sayera Banu, Deanna Hagge, Kidist Bobosha, Tom Ottenhoff, Matteo Pellegrini, Annemieke Geluk, Robert L. Modlin Reversal reactions (RRs) in leprosy are characterized by a reduction in the number of bacilli in lesions associated with an increase in cell-mediated immunity against the intracellular bacteriumMycobacterium leprae, the causative pathogen of leprosy. To identify the mechanisms that contribute to cell-mediated immunity in leprosy, we measured changes in the whole blood-derived transcriptome of patients with leprosy before, during and after RR. We identified an ‘RR signature’ of 1017 genes that were upregulated at the time of the clinical diagnosis of RR. Using weighted gene correlated network analysis (WGCNA), we detected a module of 794 genes,bisque4, that was significantly correlated with RR, of which 434 genes were part of the RR signature. An enrichment for both IFN- γ and IFN-β downstream gene pathways was present in the RR signature as well as the RR upregulated genes in thebisque4 module, including those encoding proteins of the guanylate binding protein (GBP) family that contributes to antimicrobial responses against mycobacteria. Specifically,GBP1,GBP2,GBP3 andGBP5 mRNAs were upregulated in the RR peripheral blood transcriptome, withGBP1,GBP2 andGBP5 mRNAs also upregulated in the RR disease lesion transcriptome. These data indicate that RRs involve a systemic upregulation of IFN- ...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research