Evolving immunometabolic response to the early Leishmania infantum infection in the spleen of BALB/c mice described by gene expression profiling

Palacios, Génesis; Diaz-Solano, Raquel; Valladares, Basilio; Dorta-Guerra, Roberto; Carmelo, Emma

doi:10.1016/j.actatropica.2023.107005

Cited by 2 publications

(1 citation statement)

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“…Notably, the functional enrichment analysis evidenced SREBP-related terms (i.e., Activation of gene expression by SREBF; Regulation of cholesterol biosynthesis by SREBP; SREBP signaling; SREBF and miR33 in cholesterol and lipid homeostasis) in the downregulated set of genes either at 24h and 48h post-infection ( S6 Table ). Alterations in host cell lipid metabolic pathways have been reported in previous studies on murine models, highlighting the close relationship among host lipid metabolism, immune response, and the prognosis of the disease [ 58 , 59 ].…”

Section: Resultsmentioning

confidence: 94%

Transcriptional signatures in human macrophage-like cells infected by Leishmania infantum, Leishmania major and Leishmania tropica

Diotallevi,

Bruno,

Castelli

et al. 2024

PLoS Negl Trop Dis

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Background In the Mediterranean basin, three Leishmania species have been identified: L. infantum, L. major and L. tropica, causing zoonotic visceral leishmaniasis (VL), zoonotic cutaneous leishmaniasis (CL) and anthroponotic CL, respectively. Despite animal models and genomic/transcriptomic studies provided important insights, the pathogenic determinants modulating the development of VL and CL are still poorly understood. This work aimed to identify host transcriptional signatures shared by cells infected with L. infantum, L. major, and L. tropica, as well as specific transcriptional signatures elicited by parasites causing VL (i.e., L. infantum) and parasites involved in CL (i.e., L. major, L. tropica). Methodology/Principal findings U937 cells differentiated into macrophage-like cells were infected with L. infantum, L. major and L. tropica for 24h and 48h, and total RNA was extracted. RNA sequencing, performed on an Illumina NovaSeq 6000 platform, was used to evaluate the transcriptional signatures of infected cells with respect to non-infected cells at both time points. The EdgeR package was used to identify differentially expressed genes (fold change > 2 and FDR-adjusted p-values < 0.05). Then, functional enrichment analysis was employed to identify the enriched ontology terms in which these genes are involved. At 24h post-infection, a common signature of 463 dysregulated genes shared among all infection conditions was recognized, while at 48h post-infection the common signature was reduced to 120 genes. Aside from a common transcriptional response, we evidenced different upregulated functional pathways characterizing L. infantum-infected cells, such as VEGFA-VEGFR2 and NFE2L2-related pathways, indicating vascular remodeling and reduction of oxidative stress as potentially important factors for visceralization. Conclusions The identification of pathways elicited by parasites causing VL or CL could lead to new therapeutic strategies for leishmaniasis, combining the canonical anti-leishmania compounds with host-directed therapy.

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Section: Resultsmentioning

confidence: 94%