Parasites, Hosts and Diseases

The Korea Society for Parasitology and Tropical Medicine (대한기생충학·열대의학회)
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Hypoxia-Inducible Factor-1 Alpha Stabilization in Human Macrophages during Leishmania major Infection Is Impaired by Parasite Virulence

  • Ben-Cheikh, Ali (Institut Pasteur de Tunis, LR16IPT02, Laboratory of Transmission, Control and Immunobiology of Infections (LTCII)) ;
  • Bali, Aymen (Institut Pasteur de Tunis, LR16IPT02, Laboratory of Transmission, Control and Immunobiology of Infections (LTCII)) ;
  • Guerfali, Fatma Z (Institut Pasteur de Tunis, LR16IPT02, Laboratory of Transmission, Control and Immunobiology of Infections (LTCII)) ;
  • Atri, Chiraz (Institut Pasteur de Tunis, LR16IPT02, Laboratory of Transmission, Control and Immunobiology of Infections (LTCII)) ;
  • Attia, Hanene (Institut Pasteur de Tunis, LR16IPT02, Laboratory of Transmission, Control and Immunobiology of Infections (LTCII)) ;
  • Laouini, Dhafer (Institut Pasteur de Tunis, LR16IPT02, Laboratory of Transmission, Control and Immunobiology of Infections (LTCII))
  • Received : 2022.05.08
  • Accepted : 2022.06.27
  • Published : 2022.10.31
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Abstract

Hypoxia-inducible factor-1 alpha (HIF-1α) is one of the master regulators of immune and metabolic cellular functions. HIF-1α, a transcriptional factor whose activity is closely related to oxygen levels, is a target for understanding infectious disease control. Several studies have demonstrated that HIF-1α plays an important role during the infectious process, while its role in relation to parasite virulence has not been addressed. In this work, we studied the expression levels of HIF-1α and related angiogenic vascular endothelial growth factor A (VEGF-A) in human macrophages infected with promastigotes of hypo- or hyper-virulent Leishmania major human isolates. L. major parasites readily subverted host macrophage functions for their survival and induced local oxygen consumption at the site of infection. In contrast to hypo-virulent parasites that induce high HIF-1α expression levels, hyper-virulent L. major reduced HIF-1α expression in macrophages under normoxic or hypoxic conditions, and consequently impeded the expression of VEGF-A mRNA. HIF-1α may play a key role during control of disease chronicity, severity, or outcome.

Keywords

Acknowledgement

This work was supported by the Tunisian Ministry of Higher Education and Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank the Animal Facilities of the Institut Pasteur de Tunis for their help conducting this study.

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