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.

Keywords: MIF; cytokine; host-parasite interaction; immune evasion; immunopathology; immunotherapeutic target; protozoan parasites.

Figure 1

Host-parasite interaction involving protozoa-produced macrophage migration inhibitory factor (MIF). Protozoa secrete MIF that is structurally similar to human MIF. Protozoa MIF binds directly to the human MIF receptor CD74, activating the ERK pathway with immunomodulatory effects on variety of immune and epithelial cells. Protozoa MIF immunomodulatory effects appear to play a role in parasite invasion and immune evasion, and has been linked to pathogenesis.

Figure 2

E. histolyica MIF (EhMIF) in human amebiasis. (A) Children in the top 50th percentile for anti- EhMIF antibody (blue line) had a significantly higher probability of survival free of E. histolytica infection than children within lower 50th percentile (red line). (B) Significant positive correlation between fecal EhMIF levels and the myeloperoxidase (MPO) marker of intestinal inflammation in persons with amebiasis (n = 35). Panels are reproduced from (17) with permission.