Parasite-Produced MIF Cytokine: Role in Immune Evasion, Invasion, and Pathogenesis

Abstract

Protozoan parasites represent a major threat to health and contribute significantly to morbidity and mortality worldwide, especially in developing countries. This is further compounded by lack of effective vaccines, drug resistance and toxicity associated with current therapies. Multiple protozoans, including Plasmodium, Entamoeba, Toxoplasma , and Leishmania produce homologs of the cytokine MIF. These parasite MIF homologs are capable of altering the host immune response during infection, and play a role in immune evasion, invasion and pathogenesis. This minireview outlines well-established and emerging literature on the role of parasite MIF homologs in disease, and their potential as targets for therapeutic and preventive interventions.

Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair

“…These MIF homologs are structurally and functionally similar to human MIF and interact with CD74. While it may seem counter-intuitive for protozoans to secrete MIF, parasite MIF appears to contribute to immune evasion and invasion (31)(32)(33).…”

Role of Host and Parasite MIF Cytokines during Leishmania Infection

“…From these studies there emerges a paradigm in which parasite MIFs augment the host immune response in a manner that preserves the parasite niche and prevents development of long-term immunity. The properties of over 20 MIF orthologs encoded by protozoan and helminthic parasites have been explored and reported on, and like L. major-encoded MIF these closely replicate many of the activities of mammalian MIF [101,102,[106][107][108]. While Leishmania and Plasmodium-encoded MIF orthologs promote an inflammatory state, Th1-type response, orthologs of various helminthic pathogens drive an immunosuppressive, Th2-type response.…”

“…The discovery of Leishmania-encoded MIF orthologs is not entirely surprising, as MIF orthologs are found in organisms at all positions of the evolutionary tree, including protozoa, nematodes, plants, and invertebrate and vertebrate mammals alike. Furthermore, MIF orthologs have been reported in dozens of species of protozoan and helminthic parasites, and their properties have been thoroughly explored [100][101][102].…”

Atypical Membrane-Anchored Cytokine MIF in a Marine Dinoflagellate

“…The possible occurrence of a transmembrane cytokine in a free living unicellular eukaryote would be unexpected, as MIFs are typically soluble proteins that are stored in vesicles of immune and non-immune cells, and massively secreted upon challenge [ 3 , 8 , 9 , 10 , 11 ]. In addition, previous studies on MIFs from unicellular species have been restricted to parasitic protists [ 12 ] such as Plasmodium species [ 13 ], Leishmania , [ 14 ], or Entamoeba histolitica [ 15 ]. MIFs from these species are secreted into the blood of the vertebrate host and participate in immune evasion and pathogenesis [ 12 , 16 ].…”

“…In addition, previous studies on MIFs from unicellular species have been restricted to parasitic protists [ 12 ] such as Plasmodium species [ 13 ], Leishmania , [ 14 ], or Entamoeba histolitica [ 15 ]. MIFs from these species are secreted into the blood of the vertebrate host and participate in immune evasion and pathogenesis [ 12 , 16 ]. The aim of this study was therefore to investigate the existence of a transmembrane MIF protein in the dinoflagellate L. polyedra , and to start exploring its potential function.…”