Innate immune activation and subversion of Mammalian functions by leishmania lipophosphoglycan

Abstract

Leishmania promastigotes express several prominent glycoconjugates, either secreted or anchored to the parasite surface. Of these lipophosphoglycan (LPG) is the most abundant, and along with other phosphoglycan-bearing molecules, plays important roles in parasite infectivity and pathogenesis in both the sand fly and the mammalian host. Besides its contribution for parasite survival in the sand fly vector, LPG is important for modulation the host immune responses to favor the establishment of mammalian infection. This review will summarize the current knowledge regarding the role of LPG in Leishmania infectivity, focusing on the interaction of LPG and innate immune cells and in the subversion of mammalian functions by this molecule.

Figure 1

Structure of Lipophosphoglycan from Leishmania donovani. The four key domains (cap, phosphoglycan repeating units, glycan core and lipid anchor) are discussed further in the text. The number of phosphoglycan (PG) repeating units increases during metacyclogenesis, contributing to the role of LPG in complement resistance. In many Leishmania species, side chain modifications of the PG Gal residue are common, where they can play a role in sand fly transmission. The structure of the cap also differs amongst species. Gal, galactose; Man; Mannose; GN, glucosamine; Glc, glucose.

Figure 2

Role of LPG in Leishmania infectivity and virulence. Shown are putative and bona fide actions of Leishmania spp. LPG molecules in subversion of host and vector functions. These LPG functions include (1) physical protection to promastigotes against hydrolytic enzymes in the digestive tract of insect; (2) attachment of promastigotes to the gut wall; (3) In the mammalian host, promastigotes protection against lysis by complement proteins; (4) attachment of parasites to the macrophage membranes or alternative transiently infected cells, such as neutrophils, dendritic cells and perhaps others; (5) transient impairment of the phagosome maturation; (6) physical protection against degradation by lysosomal enzymes; (7) modulation of macrophages activation through impairing the synthesis of nitrogen species and cytokines related to the control of infection and protection from ROS.