2024 March 05; 36(3): 484–497.e6. doi:10.1016/j.cmet.2024.01.008. | Theresa Ramalho, Patricia A. Assis, Ogoluwa Ojelabi, Lin Tan, Brener Carvalho, Luiz Gardinassi, Osvaldo Campos, Philip L. Lorenzi, Katherine A. Fitzgerald, Cole Haynes, Douglas T. Golenbock, Ricardo T. Gazzinelli
The study investigates the role of itaconate in enhancing immune control of *Plasmodium* by monocyte-derived dendritic cells (MODCs). Itaconate, a代谢产物, is accumulated in MODCs during malaria infection due to increased glycolysis and disruption of the tricarboxylic acid (TCA) cycle. This accumulation leads to mitochondrial dysfunction, which results in the release of degraded mitochondrial DNA (mtDNA) into the cytosol. The mtDNA then activates the STING-IRF3/IRF7 pathway, promoting the expression of PD-L1 on MODCs. This expression of PD-L1 impairs the activation of CD8+ T cells, leading to reduced parasite clearance and increased parasitemia. The study suggests that targeting the ACOD1 enzyme, which converts aconitate to itaconate, could enhance immune response against *Plasmodium* and improve the efficacy of antimalarial therapies.The study investigates the role of itaconate in enhancing immune control of *Plasmodium* by monocyte-derived dendritic cells (MODCs). Itaconate, a代谢产物, is accumulated in MODCs during malaria infection due to increased glycolysis and disruption of the tricarboxylic acid (TCA) cycle. This accumulation leads to mitochondrial dysfunction, which results in the release of degraded mitochondrial DNA (mtDNA) into the cytosol. The mtDNA then activates the STING-IRF3/IRF7 pathway, promoting the expression of PD-L1 on MODCs. This expression of PD-L1 impairs the activation of CD8+ T cells, leading to reduced parasite clearance and increased parasitemia. The study suggests that targeting the ACOD1 enzyme, which converts aconitate to itaconate, could enhance immune response against *Plasmodium* and improve the efficacy of antimalarial therapies.