Immunomodulation by Leishmania parasites: Potential for controlling other diseases

In the mammalian hosts, Leishmania parasites survive and proliferate within phagolysosomes of macrophages. To avoid being killed by the immune cells, Leishmania parasites utilize their molecules to manipulate macrophages' functions for survival. Targets of such immunomodulatory molecules are not limited to macrophages, as Leishmania-derived molecules sometimes show influence on other immune cells such as neutrophils, dendritic cells, T cells and B cells. This review covers research on immunomodulation of host immunity by Leishmania parasites and introduces some examples of parasite-derived molecules participating in the immunomodulation. For example, Leishmania cell surface lipophosphoglycan (LPG) can modulate TLR2 signaling and PI3K/Akt axis in macrophages leading to induction of Th2 cells. Because chronic secretion of inflammatory cytokines is one of the causes of immune-mediated diseases such as atherosclerosis, Crohn's disease, and rheumatoid arthritis, LPG may be useful as a drug to suppress the inflammatory conditions. The unique characteristics of leishmanial molecules pose a promise as a source of immunomodulatory drugs for controlling diseases other than leishmaniasis.