Jpn. J. Infect. Dis., 58, 131-148, 2005
To see a printable version of the article in the Adobe file format, click this [PDF] link.
Invited Review
Sphingolipids in Infectious Diseases
Kentaro Hanada*
Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
(Received January 26, 2005)
*Corresponding author: Mailing address: Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan. Tel: +81-3-5285-1111 ext. 2126, Fax: +81-3-5285-1157, E-mail: hanak@nih.go.jp
CONTENTS:
1. Introduction
2. Structure and biosynthesis of sphingolipids
3. Sphingolipids act as membrane receptors of various pathogens
3-1. Receptors for protein toxins
3-1-1. AB toxins
3-1-1-1. Cholera-like toxins
3-1-1-2. Shiga-like toxins
3-1-1-3. Tetanus and botulinum neurotoxins
3-1-2. Non-AB toxin
3-2. Receptors for viruses
3-2-1. Human immunodeficiency virus type 1
3-2-2. Influenza virus and others
3-3. Receptors for bacteria and fungi
3-3-1. Fimbriated Escherichia coli
3-3-1-1. P-fimbriated E. coli
3-3-1-2. F1C-fimbriated E. coli
3-3-1-3. S-fimbriated E. coli
3-3-2. Various pulmonary pathogenic bacteria
3-3-3. Helicobacter pylori
3-3-4. Candida albicans
4. Sphingolipids involved in pathogen induced signaling
4-1. Signaling induced by pathogen-mediated clustering of sphingolipids
4-2. Ceramide production in response to infection
4-3. Glycosphingolipid-mediated signaling with transmembrane co-receptors
5. Sphingolipids for the formation of detergent-resistant membrane
domains, lipid-rafts
5-1. Conversion of prions to their pathogenic conformers
5-2. Induction of efficient entry of anthrax toxin
5-3. Invasion and intracellular growth of Chlamydia
5-4. Contact and entry of Shigella
5-5. Entry of type 1-fimbriated E. coli into bladder
epithelium
5-6. Modulation of translocation of diphtheria toxin across membranes
6. Sphingolipid/cholesterol-dependent but raft-independent fusion
of Semliki Forest virus and Sindbis virus
7. Sphingolipids in postinfectious auto-immune diseases
7-1. Guillain-Barre syndrome
7-2. Miller-Fisher syndrome
8. Self-ligands for CD1d-restricted natural killer T cells
9. Sphingolipids in microbes as anti-infectious disease targets
9-1. Anti-fungal targets
9-2. Anti-protozoan targets
10. Conclusions and perspectives
SUMMARY: Sphingolipids are ubiquitous constituents of membrane lipids in eukaryotes. Sphingolipid metabolites modulate various cellular events including proliferation, differentiation, and apoptosis. In addition, sphingolipids, along with cholesterol, form detergent-resistant membrane microdomains, so called 'lipid-rafts', which are implicated in signal transduction and membrane trafficking. Sphingolipids are also relevant to infectious diseases. Various types of pathogens exploit the sphingolipids of host cells as membrane receptors. Sphingolipid metabolites regulate pathogen infection and host defense: for instance, a specific glycosphingolipid acts as an endogenous ligand for activation of natural killer T cells. Lipid-rafts of host cells serve as platforms also for infection signaling and entry of intracellular parasites. Moreover, some post-infectious autoimmune diseases result from production of antibodies cross-reacting with mammalian sphingolipids. Differences in the pathways of sphingolipid metabolism between mammals and non-mammals are good clues for rational development of new anti-infectious disease drugs. This review summarizes recent advances in sphingolipid biology related to infectious diseases.