Itaconate boosts malaria via induction of PD-L1

The Krebs-cycle-derived metabolite itaconate has been shown to be immunomodulatory, targeting multiple processes in macrophages. Ramalho et al. reveal an additional role for itaconate in malaria. 1 Ramalho T. Assis P.A. Ojelabi O. Tan L. Carvalho B. Gardinassi L. Campos O. Lorenzi P.L. Fitzgerald K.A. Haynes C. et al. Itaconate impairs immune control of Plasmodium by enhancing mtDNA-mediated PD-L1 expression in monocyte-derived dendritic cells. Cell Metabol. 2024; 36: 484-497 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar Plasmodium Chabaudi induces itaconate in dendritic cells (DCs), leading to programmed death-ligand 1 (PD-L1) induction. This suppresses CD8+ T cells, important for host defense against malaria, thereby promoting parasitemia. The Krebs-cycle-derived metabolite itaconate has been shown to be immunomodulatory, targeting multiple processes in macrophages. Ramalho et al. reveal an additional role for itaconate in malaria. 1 Ramalho T. Assis P.A. Ojelabi O. Tan L. Carvalho B. Gardinassi L. Campos O. Lorenzi P.L. Fitzgerald K.A. Haynes C. et al. Itaconate impairs immune control of Plasmodium by enhancing mtDNA-mediated PD-L1 expression in monocyte-derived dendritic cells. Cell Metabol. 2024; 36: 484-497 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar Plasmodium Chabaudi induces itaconate in dendritic cells (DCs), leading to programmed death-ligand 1 (PD-L1) induction. This suppresses CD8+ T cells, important for host defense against malaria, thereby promoting parasitemia. Itaconate impairs immune control of Plasmodium by enhancing mtDNA-mediated PD-L1 expression in monocyte-derived dendritic cellsRamalho et al.Cell MetabolismFebruary 6, 2024In BriefRamalho et al. unveil that splenic monocyte-derived dendritic cells (MODCs) accumulate TCA cycle-derived itaconate in experimental malaria. Itaconate-induced mitochondrial disruption releases nucleic acids, which activate STING-IRF3/IRF7-mediated expression of PD-L1. In such a state, MODCs expressing PD-L1 impair imune-mediated control of Plasmodium by limiting the activation of CD8+ lymphocytes. Full-Text PDF Open Access