Lipids in host-pathogen interactions: pathogens exploit the complexity of the host cell lipidome

Abstract

Lipids were long believed to have a structural role in biomembranes and a role in energy storage utilizing cellular lipid droplets and plasma lipoproteins. Research over the last decades has identified an additional role of lipids in cellular signaling, membrane microdomain organization and dynamics, and membrane trafficking. These properties make lipids an attractive target for pathogens to modulate host cell processes in order to allow their survival and replication. In this review we will summarize the often ingenious strategies of pathogens to modify the lipid homeostasis of host cells, allowing them to divert cellular processes. To this end pathogens take full advantage of the complexity of the lipidome. The examples are categorized in generalized and emerging principles describing the involvement of lipids in host-pathogen interactions. Several pathogens are described that simultaneously induce multiple changes in the host cell signaling and trafficking mechanisms. Elucidation of these pathogen-induced changes may have important implications for drug development. The emergence of high-throughput lipidomic techniques will allow the description of changes of the host cell lipidome at the level of individual molecular lipid species and the identification of lipid biomarkers.

Fig. 1

Overview of modifications of the host cell lipidome by various pathogens. MVB: multivesicular body; EPEC: Enteropathogenic E. coli; PC: phosphatidylcholine; PI: phosphatidylinositol; PI(3)P: phosphatidylinositol-3-phosphate; PI(5)P: phosphatidylinositol-5-phosphate; PI(3,4)P₂: phosphatidylinositol-3,4-bisphosphate; PI(4,5)P₂: phosphatidylinositol-4,5-bisphosphate; PI(3,4,5)P₃: phosphatidylinositol-3,4,5-trisphosphate.

Fig. 2

Lipid metabolism at the pathogen-containing vacuole. The various effectors and enzymes are drawn in the vacuolar membrane. However, their exact location relative to the membrane is, in most cases, unknown. PLA: phospholipase A1 or A2; PLC: phospholipase C; PLD: phospholipase D; PL: phospholipid; PA: phosphatidic acid; DAG: diacylglycerol; Sph: sphingosine; S1P: sphingosine-1-phosphate; RSV: respiratory syncytial virus; CMV: cytomegalovirus; Chol: cholesterol; LDL: low-density lipoprotein; EspF: Escherichia coli effector molecule F; SapM: M. tuberculosis effector molecule; IpgD: Shigella flexneri effector molecule; SseJ: Salmonella SPI-2 effector molecule; Lda: Lipid droplet-associated Chlamydial effector proteins. For other abbreviations: see legend to Fig. 1.

Fig. 3

Effects of Toxoplasma gondii on the host cell lipidome. ACAT: acyl-CoA:cholesterol acyltransferase; ER: endoplasmic reticulum; LDL: low-density lipoprotein; CE: cholesterolester.

Fig. 4

Effects of mycobacteria on the host cell lipidome. LD: lipid droplet; S1P: sphingosine-1-phosphate; SapM: M. tuberculosis effector molecule; PI(3)P: phosphatidylinositol-3-phosphate; EEA1: Early endosomal antigen 1; PI(3)K/Vps34: phosphoinositide 3- kinase; PIM: phosphatidylinositol mannoside; ManLam: mannose-capped form of Lam (lipoarabinomannan); ER: endoplasmic reticulum; TACO: tryptophan aspartate containing coat protein.

Fig. 5

Effects of Chlamydia trachomatis on the host cell lipidome. LD: lipid droplet; DAG: diacylglycerol; ER: endoplasmic reticulum; MVB: multivesicular body.