Itaconate: A Nexus Metabolite Fueling <i>Leishmania</i> Survival Through Lipid Metabolism Modulation
Leishmaniasis, caused by the <i>Leishmania</i> parasite, is a neglected public health issue. <i>Leishmania</i> mainly infects macrophages, where metabolic reprogramming shapes their plasticity (M1/M2), affecting the host’s resistance or susceptibility to infection. The develo...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-02-01
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| Series: | Microorganisms |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-2607/13/3/531 |
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| Summary: | Leishmaniasis, caused by the <i>Leishmania</i> parasite, is a neglected public health issue. <i>Leishmania</i> 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 <i>Acod1</i> 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 <i>L. major</i>-infected BMDMs, we assessed the expression dynamics of <i>Il1b</i> and <i>Acod1</i> and performed pathway enrichment analysis to determine the profile of genes co-expressed with <i>Acod1</i>. Early <i>Acod1</i> upregulation followed by later <i>Il1b</i> downregulation was noted, indicating a shift towards an anti-inflammatory response. Among the genes co-expressed with <i>Acod1</i>, <i>Ldlr</i>, <i>Hadh</i>, and <i>Src</i> are closely associated with lipid metabolism and the polarization of macrophages towards the M2 phenotype, thereby creating a favorable environment for the survival of <i>Leishmania</i>. Overall, these findings suggest that <i>Acod1</i> and its co-expressed genes may affect the outcome of <i>Leishmania</i> infection by modulating host metabolism. Accordingly, targeting itaconate-associated pathways could provide a novel therapeutic strategy for leishmaniasis. |
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| ISSN: | 2076-2607 |