Role of Host and Parasite MIF Cytokines during <i>Leishmania</i> Infection

• Main Authors: Thomas Holowka, Richard Bucala
• Format: Article
• Language: English
• Published: MDPI AG 2020-03-01
• Series: Tropical Medicine and Infectious Disease
• Subjects: <i>leishmania</i>; mif; inflammation; immunization
• Online Access: https://www.mdpi.com/2414-6366/5/1/46

Macrophage migration inhibitory factor (MIF) is an immunoregulatory cytokine that has been extensively characterized in human disease and in mouse models. Its pro-inflammatory functions in mammals includes the retention of tissue macrophages and a unique ability to counteract the immunosuppressive activity of glucocorticoids. MIF also acts as a survival factor by preventing activation-induced apoptosis and by promoting sustained expression of inflammatory factors such as TNF-&#945; and nitric oxide. The pro-inflammatory activity of MIF has been shown to be protective against <i>Leishmania major</i> infection in mouse models of cutaneous disease, however the precise role of this cytokine in human infections is less clear. Moreover, various species of <i>Leishmania</i> produce their own MIF orthologs, and there is evidence that these may drive an inflammatory environment that is detrimental to the host response. Herein the immune response to <i>Leishmania</i> in mouse models and humans will be reviewed, and the properties and activities of mammalian and <i>Leishmania</i> MIF will be integrated into the current understandings in this field. Furthermore, the prospect of targeting <i>Leishmania</i> MIF for therapeutic purposes will be discussed.