Gene Expression Profiling of Classically Activated Macrophages in Leishmania infantum Infection: Response to Metabolic Pre-Stimulus with Itaconic Acid

  1. Palacios, Génesis 1
  2. Vega-García, Elva 1
  3. Valladares, Basilio 13
  4. Pérez, José Antonio 14
  5. Dorta-Guerra, Roberto 12
  6. Carmelo, Emma 13
  1. 1 Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUESTPC), Universidad de La Laguna (ULL), Avenida Astrofísico Francisco Sánchez s/n, 38200 La Laguna, Tenerife, Spain
  2. 2 Departamento de Matemáticas, Estadística e Investigación Operativa, Facultad de Ciencias, Universidad de La Laguna, 38200 La Laguna, Tenerife, Spain
  3. 3 Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud PÚblica, Toxicología, Medicina Legal y Forense y Parasitología, Universidad de La Laguna, 38200 La Laguna, Tenerife, Spain
  4. 4 Departamento de Bioquímica, Microbiología, Biología Celular y Genética, Facultad de Ciencias, Universidad de La Laguna, 38200 La Laguna, Tenerife, Spain
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Revista:
Tropical Medicine and Infectious Disease

ISSN: 2414-6366

Año de publicación: 2023

Volumen: 8

Número: 5

Páginas: 264

Tipo: Artículo

DOI: 10.3390/TROPICALMED8050264 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Tropical Medicine and Infectious Disease

Resumen

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.

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Información de financiación

Financiadores

  • Universidad de La Laguna
  • Fundación Canaria para el Control de Enfermedades Tropicales
  • Canarias de la Consejería de Economía, Industria, Comercio y Conocimiento
    • TESIS2019010018

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