African trypanosomes are extracellular flagellated unicellular protozoan parasites transmitted by tsetse flies and causing Sleeping Sickness disease in humans and
Nagana disease in cattle and other livestock. These diseases are usually characterized by the development of a fatal chronic inflammatory disease if left untreated. During African trypanosome
infection and many other
infectious diseases, the immune response is mediating a see-saw balance between effective/protective immunity and excessive
infection-induced
inflammation that can cause collateral tissue damage. African trypanosomes are known to trigger a strong type I pro-inflammatory response, which contributes to peak parasitaemia control, but this can culminate into the development of immunopathologies, such as anaemia and liver injury, if not tightly controlled. In this context, the
macrophage migration inhibitory factor (MIF) and the
interleukin-10 (IL-10)
cytokines may operate as a molecular "Yin-Yang" in the modulation of the host immune microenvironment during African trypanosome
infection, and possibly other
infectious diseases. MIF is a pleiotropic pro-inflammatory
cytokine and critical upstream mediator of immune and inflammatory responses, associated with exaggerated
inflammation and immunopathology. For example, it plays a crucial role in the pro-inflammatory response against African trypanosomes and other pathogens, thereby promoting the development of immunopathologies. On the other hand,
IL-10 is an anti-inflammatory
cytokine, acting as a master regulator of
inflammation during both
African trypanosomiasis and other diseases.
IL-10 is crucial to counteract the strong MIF-induced pro-inflammatory response, leading to pathology control. Hence, novel strategies capable of blocking MIF and/or promoting
IL-10 receptor signaling pathways, could potentially be used as
therapy to counteract immunopathology development during African trypanosome
infection, as well as during other infectious conditions. Together, this review aims at summarizing the current knowledge on the opposite immunopathological molecular "Yin-Yang" switch roles of MIF and
IL-10 in the modulation of the host immune microenvironment during
infection, and more particularly during
African trypanosomiasis as a paradigm.