Guanylate Binding Proteins promote anti-Leishmania Host Cell Defense

Abstract

Leishmania donovani is an obligatory intracellular protozoa pathogen that transmits by sand flies to mammalian hosts. L. donovani is the causative agent of the disease Visceral Leishmaniasis (VL), also known as Kala-azar, which causes hepatosplenomegaly i.e., enlargement of the spleen and liver in patients. The VL is regarded as one of the most devastating neglected infectious diseases in tropical and sub-tropical regions and can be fatal if the patients left untreated [1]. Professional phagocytic cells (e.g., macrophages, dendritic cells, neutrophils) are considered to be the most important host cells for L. donovani for its survival and replication [2-4]. However, several in vitro and in vivo studies have shown that non-phagocytic cell types like epithelial cells and fibroblasts [5-7] endocytose L. donovani. Despite the significance of these findings, little attempt has been made to address the questions: 1) How these non-phagocytic cells restrict parasite growth? 2) Does it depend on an interferon-induced pathway? 3) If not, then how do nonphagocytic cells control this pathogen? In a recent study, we discovered that non-phagocytic cells have intrinsic properties that limit L. donovani growth even in the absence of interferon-gamma (IFNγ) stimulation via an autophagy mediated non-canonical pathway [6].