Role of Lipid Rafts in Pathogen-Host Interaction - A Mini Review

Abstract

Lipid rafts, also known as microdomains, are important components of cell membranes and are enriched in cholesterol, glycophospholipids and receptors. They are involved in various essential cellular processes, including endocytosis, exocytosis and cellular signaling. Receptors are concentrated at lipid rafts, through which cellular signaling can be transmitted. Pathogens exploit these signaling mechanisms to enter cells, proliferate and egress. However, lipid rafts also play an important role in initiating antimicrobial responses by sensing pathogens via clustered pathogen-sensing receptors and triggering downstream signaling events such as programmed cell death or cytokine production for pathogen clearance. In this review, we discuss how both host and pathogens use lipid rafts and associated proteins in an arms race to survive. Special attention is given to the involvement of the major vault protein, the main constituent of a ribonucleoprotein complex, which is enriched in lipid rafts upon infection with vaccinia virus.

Keywords: cell entry; lipid rafts; major vault protein; pathogen-host interactions; vaccinia virus.

Figure 1

Biological roles of lipid rafts in pathogen-host interactions: (A) Lipid rafts are involved in several cellular functions, such as pathogen recognition, cell signaling, and pathogen egress which decides the outcome of pathogen-host interaction. (B) Lipid rafts in pathogen sensing and cytokine release: Lipid rafts play an important role in pathogen sensing by recruiting pathogen sensing receptors such as toll like receptors when cells are stimulated with bacterial cell wall components LPS or LTA and C-type lectin receptors when stimulated with fungal cell wall components such as β-glucans which evetually leads to cytokine secretion.

Figure 2

MVP accumulates in lipid rafts after infection with vaccinia virus (A) Schematic representation of differential IMID-H4/D4 labeling and LC/MS/MS analyses of lipid raft-associated proteins isolated from HeLa cells that were either mock infected or infected with WR strain MV as previously described (66, 67). (CNBr, Cyanogen bromide, SCX, Strong cation exchange column, m/z, mass-to-charge ratio), (B) Differential protein association in lipid raft proteome derived from mock or vaccinia virus infected HeLa cells (66). Labelled peptides were quantitatively determined by lysine-specific isotope labeling scheme. Co-eluted peaks contained peptides from both virus infected cells (blue) and from mock-infected cells (red). The blue-to-red ratio determined whether abundance of one particular peptide after virus infection is increased (>1), unchanged (=1) or decreased (<1). (C) Role of MVP in signaling pathways: MVP protein, the major component of vault particle, is recruited to the lipid rafts upon stimulation with growth factors (e.g., EGF) or pathogen derived ligands (e.g., LPS) and regulates important biological processes such as cell proliferation and cytokine secretion. IFNAR receptor stimulation with IFN-γ in the lipid rafts activates JAK-STAT signaling pathway which in turn will lead to the transcription of MVP. MVP also plays an important role in regulating apoptotic signaling pathway on infection with pathogens such as P. aeruginosa and helps in host protection, however the detailed mechanism on how recruitment of MVP to the lipid rafts after infection with other pathogens such as VacV, EBV and influenza virus needs investigation.