Gene expression profiling of classically activated macrophages in 'Leishmania infantum' infection: Response to metabolic pre-stimulus with itaconic acid

'Leishmania' infection of phagocytic cells, such as macrophages, induces the differentiation of infected cells into different phenotypes according to their surrounding microenvironments. The classical activation of macrophages involves metabolic reprogramming, in which several metabolites...

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Bibliographic Details
Published in:Tropical medicine and infectious disease 2023-05, Vol.8 (5), p.1-S12
Main Authors: Genesis Palacios, Elva Vega-Garcia, Basilio Valladares, Jose Antonio Perez, Roberto Dorta-Guerra, Emma Carmelo
Format: Article
Language:English
Subjects:
Acids
Bone marrow
classically activated macrophages
Complications
Diagnosis
Gene expression
gene expression profiling
Immunological aspects
Infection
Infections
itaconate
Leishmania
Leishmania infantum
Leishmaniasis
macrophage activation
metabolic stimulus
Metabolism
Metabolites
Parasites
Parasitic diseases
Penicillin
Phosphorylation
Technique
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Summary:'Leishmania' infection of phagocytic cells, such as macrophages, induces the differentiation of infected cells into different phenotypes according to their surrounding microenvironments. The classical activation of macrophages involves metabolic reprogramming, in which several metabolites such as succinate, fumarate and itaconate are accumulated. The immunoregulatory functions of itaconate in the context of 'Leishmania' infection were investigated in this paper. Ex vivo bone marrow-derived macrophages were differentiated into classically activated macrophages through IFNG activation and infection with 'Leishmania infantum'. A high-throughput real-time qPCR experiment was designed for the analyses of 223 genes involved in immune response and metabolism. The transcriptional profile of classically activated macrophages revealed the enrichment of the IFNG response pathways and the upregulation of genes such as 'Cxcl9, Irf1, Acod1, Il12b, Il12rb1, Nos2'or 'Stat1'. In vitro pre-stimulation with itaconate induced a loss of the parasite control and the upregulation of genes related to local acute inflammatory response. Our results reveal that itaconate accumulation dampened classically activated macrophage antiparasitic activity, and this is reflected by the differential expression of the 'Il12b, Icosl' and 'Mki67' genes. The possibility of inducing parasite-killing responses in the host through metabolic reprograming is an interesting approach for the treatment of 'Leishmania' infections that will undoubtedly attract increasing attention in the coming years.
ISSN:2414-6366
2414-6366
DOI:10.3390/tropicalmed8050264