Korean J Parasitol.  2022 Oct;60(5):317-325. 10.3347/kjp.2022.60.5.317.

Hypoxia-Inducible Factor-1 Alpha Stabilization in Human Macrophages during Leishmania major Infection Is Impaired by Parasite Virulence

• Ben-Cheikh A
• Bali A
• Guerfali FZ
• Atr C
• Attia H
• Laouini D

• KMID: 2535998
• DOI: http://doi.org/10.3347/kjp.2022.60.5.317

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.

Keyword

macrophage; HIF-1α; VEGF-A; hypoxia; virulence