IL-27 tips the balance of immunity toward L. donovani survival. (A) L. donovani amastigotes invade hepatic macrophages (Kupffer cells). This event is followed by the invasion of leukocytes, neutrophils, monocytes, and T cells under the influence of chemotactic factors like CCL3, CCL2, and CXCL3 secreted by infected Kupffer cells. (B) These immunological reactions lead to the formation of a granuloma that is abundant in pro-inflammatory factors (IFN-γ, TNF-α, and RNI/ROS secreted by Th1 cells, NK cells, and CD8+ T cells); under such conditions L. donovani infection is resolved over time. (C) However, the abundance of IL-4 and IL-10 decreased iNOS expression, high production of IgG1/IgG2a ratio, and delayed maturation of granuloma, depletion of neutrophils results in high parasite load. (D) Elevated IL-10 secreted by Treg cells also contributes to L. donovani survival. (E) Splenic CD11chi MHC-IIhi DCs from L. donovani-infected C57BL/6 mice show high levels of IL-27.