Chyntia Díaz Acosta Poster 2024

Dr Chyntia Díaz Acosta

National University of Asuncion (IICS-UNA), Paraguay

Exploring the role of M. leprae PGL-I as a Lipid droplet-inducing molecule in Schwann cells.

Poster Abstract

The phenolic glycolipid I, PGL I, is an exclusive cell wall molecule of Mycobacterium leprae. Its trisaccharide portion not found in PGLs of other mycobacteria confers specificity. PGL I interacts with receptors involved both in the invasion of host cells and the evasion of the immune response. Complications in leprosy involve peripheral nerve lesions, which lead to highly disabling neuropathies as a result of Schwann cells (SCs) infection. In fact, M. leprae tropism towards SCs, is associated to PGL I, because of its interaction with laminin type 2, present in the basal lamina of the peripheral nerve. Previous data from our group show that M. leprae is able to induce the formation of cholesterol-rich lipid droplets (LDs). Although we observed that cholesterol was not used as a carbon source, these organelles were shown to be important for pathogen survival. In this context, we aimed to understand how PGL I, per se, could be influencing SC lipid metabolism. Using an in vitro infection model, we observed that the internalized PGL I molecule, was able to increase i) the expression of enzymes associated to fatty acid synthesis, ii) the level of the peroxisome proliferator-activated receptor gamma (PPARγ) transcription factor in the nucleus, iii) the expression of prostaglandin E2 synthase enzyme gene. Internalization of PGL I into SCs also led to induction of LDs and increase of PGE2 production. Interactome data obtained by LC-MS/MS, validated by Western Blotting suggest the interaction of PGL I with molecules of the PPAR signaling pathway as well as components of cellular response to lipids. In conclusion, PGL I seems to participate in the regulation of lipid metabolism in infected SCs. These preliminary data contribute to a better understanding of the role of glycolipids in the pathogenesis of leprosy and the development of nerve lesions.