Abstract
Leishmaniasis is a serious infectious disease caused by Leishmania parasites, predominantly affecting tropical and subtropical regions. These parasites replicate within macrophages, manipulating the host immune response and facilitating infection progression. While long non-coding RNAs (lncRNAs) are known regulators of immune function, their time-dependent roles during Leishmania major infection remain unclear. Specifically, we now highlight that this is the first time the temporal dynamics of lncRNA expression and cis-target gene interactions have been systematically analyzed in L major-infected macrophages across 4 distinct time points. This study examined the expression profiles of long non-coding RNAs (lncRNAs), potential cis-target genes, and hub genes at different time points in human macrophages infected with L major. RNA-Seq analysis identified 39,828 lncRNAs, with 2903 showing differential expression at one or more time points. As the infection progressed (4, 24, 48, and 72 hours), the number of up- and down-regulated lncRNAs showed a dramatic decrease between 24 and 48 hours, followed by a slight increase between 48 and 72 hours. Six lncRNAs (lnc-UNC5D-8, lnc-TENM3-1, DIRC3-1, lnc-MTRNR2L12-10, lnc-FAM43A-6, and AKAP2-1) were consistently differentially expressed throughout the infection timeline and may play critical roles in modulating the host immune response. Time-specific hub genes were also identified, regulating critical processes such as keratinization, epigenetic modifications, and immune responses. In particular, these genes were pivotal during the later stages of infection in maintaining tissue integrity and regulating immune responses. Early immune responses were dominated by immunoglobulin receptor activity and adaptive immune system activation. These findings highlight the critical roles of lncRNAs and hub genes in macrophage responses to Leishmania infection, offering potential targets for future therapeutic strategies.