Itaconate: A Nexus Metabolite Fueling Survival Through Lipid Metabolism Modulation.

Leishmaniasis, caused by the parasite, is a neglected public health issue. mainly infects macrophages, where metabolic reprogramming shapes their plasticity (M1/M2), affecting the host's resistance or susceptibility to infection. The development of this infection is influenced by immune responses, with an excessive anti-inflammatory reaction linked to negative outcomes through the modulation of various mediators. Itaconate, produced by the gene, is recognized for its anti-inflammatory effects, but its function in leishmaniasis is not well understood. This study aimed to investigate the potential role of itaconate in leishmaniasis. Using transcriptomic data from -infected BMDMs, we assessed the expression dynamics of and and performed pathway enrichment analysis to determine the profile of genes co-expressed with . Early upregulation followed by later downregulation was noted, indicating a shift towards an anti-inflammatory response. Among the genes co-expressed with , , , and are closely associated with lipid metabolism and the polarization of macrophages towards the M2 phenotype, thereby creating a favorable environment for the survival of . Overall, these findings suggest that and its co-expressed genes may affect the outcome of infection by modulating host metabolism. Accordingly, targeting itaconate-associated pathways could provide a novel therapeutic strategy for leishmaniasis.