Gene Expression Profiling of Classically Activated Macrophages in <i>Leishmania infantum</i> Infection: Response to Metabolic Pre-Stimulus with Itaconic Acid
<i>Leishmania</i> 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 metab...
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MDPI AG
2023-05-01
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| Series: | Tropical Medicine and Infectious Disease |
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| Online Access: | https://www.mdpi.com/2414-6366/8/5/264 |
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| author | Génesis Palacios Elva Vega-García Basilio Valladares José Antonio Pérez Roberto Dorta-Guerra Emma Carmelo |
| author_facet | Génesis Palacios Elva Vega-García Basilio Valladares José Antonio Pérez Roberto Dorta-Guerra Emma Carmelo |
| author_sort | Génesis Palacios |
| collection | DOAJ |
| description | <i>Leishmania</i> 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 <i>Leishmania</i> infection were investigated in this paper. Ex vivo bone marrow-derived macrophages were differentiated into classically activated macrophages through IFNG activation and infection with <i>Leishmania infantum</i>. 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 <i>Cxcl9</i>, <i>Irf1</i>, <i>Acod1</i>, <i>Il12b</i>, <i>Il12rb1</i>, <i>Nos2</i> or <i>Stat1</i>. 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 <i>Il12b</i>, <i>Icosl</i> and <i>Mki67</i> genes. The possibility of inducing parasite-killing responses in the host through metabolic reprograming is an interesting approach for the treatment of <i>Leishmania</i> infections that will undoubtedly attract increasing attention in the coming years. |
| first_indexed | 2024-03-11T03:15:27Z |
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| issn | 2414-6366 |
| language | English |
| last_indexed | 2024-03-11T03:15:27Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Tropical Medicine and Infectious Disease |
| spelling | doaj.art-6f259cb392be47f68a5f239634aebcc02023-11-18T03:34:11ZengMDPI AGTropical Medicine and Infectious Disease2414-63662023-05-018526410.3390/tropicalmed8050264Gene Expression Profiling of Classically Activated Macrophages in <i>Leishmania infantum</i> Infection: Response to Metabolic Pre-Stimulus with Itaconic AcidGénesis Palacios0Elva Vega-García1Basilio Valladares2José Antonio Pérez3Roberto Dorta-Guerra4Emma Carmelo5Instituto 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, SpainInstituto 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, SpainInstituto 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, SpainInstituto 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, SpainInstituto 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, SpainInstituto 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<i>Leishmania</i> 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 <i>Leishmania</i> infection were investigated in this paper. Ex vivo bone marrow-derived macrophages were differentiated into classically activated macrophages through IFNG activation and infection with <i>Leishmania infantum</i>. 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 <i>Cxcl9</i>, <i>Irf1</i>, <i>Acod1</i>, <i>Il12b</i>, <i>Il12rb1</i>, <i>Nos2</i> or <i>Stat1</i>. 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 <i>Il12b</i>, <i>Icosl</i> and <i>Mki67</i> genes. The possibility of inducing parasite-killing responses in the host through metabolic reprograming is an interesting approach for the treatment of <i>Leishmania</i> infections that will undoubtedly attract increasing attention in the coming years.https://www.mdpi.com/2414-6366/8/5/264gene expression profilingmacrophage activationclassically activated macrophagesmetabolic stimulusitaconate<i>Leishmania infantum</i> |
| spellingShingle | Génesis Palacios Elva Vega-García Basilio Valladares José Antonio Pérez Roberto Dorta-Guerra Emma Carmelo Gene Expression Profiling of Classically Activated Macrophages in <i>Leishmania infantum</i> Infection: Response to Metabolic Pre-Stimulus with Itaconic Acid Tropical Medicine and Infectious Disease gene expression profiling macrophage activation classically activated macrophages metabolic stimulus itaconate <i>Leishmania infantum</i> |
| title | Gene Expression Profiling of Classically Activated Macrophages in <i>Leishmania infantum</i> Infection: Response to Metabolic Pre-Stimulus with Itaconic Acid |
| title_full | Gene Expression Profiling of Classically Activated Macrophages in <i>Leishmania infantum</i> Infection: Response to Metabolic Pre-Stimulus with Itaconic Acid |
| title_fullStr | Gene Expression Profiling of Classically Activated Macrophages in <i>Leishmania infantum</i> Infection: Response to Metabolic Pre-Stimulus with Itaconic Acid |
| title_full_unstemmed | Gene Expression Profiling of Classically Activated Macrophages in <i>Leishmania infantum</i> Infection: Response to Metabolic Pre-Stimulus with Itaconic Acid |
| title_short | Gene Expression Profiling of Classically Activated Macrophages in <i>Leishmania infantum</i> Infection: Response to Metabolic Pre-Stimulus with Itaconic Acid |
| title_sort | gene expression profiling of classically activated macrophages in i leishmania infantum i infection response to metabolic pre stimulus with itaconic acid |
| topic | gene expression profiling macrophage activation classically activated macrophages metabolic stimulus itaconate <i>Leishmania infantum</i> |
| url | https://www.mdpi.com/2414-6366/8/5/264 |
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