Table 1.
Lipid structures involved in various pathological conditions affecting the immune system.
| Lipid Element | Protein Element | Pathogenic/Physiological Condition | Lipids Implicated in Pathogenicity | Therapeutic Approach Targeting the Lipid Fraction | Reference |
|---|---|---|---|---|---|
| Lipid rafts PUFAs |
IL-2, FcR, PKC, NF-kB, AP-1 | Altered localization of receptors, mediators and transcription factors | PUFAs | Dietary supply of PUFAs alters T- and B-lymphocyte membranes | [185] |
| Lipid rafts PUFAs |
PTKs (LCK), CD45, CD3, FcR | SLE | Increased amount of lipid rafts in activated T-cells | - | [185] |
| PE | Atg8/LC3 | Double membrane formation of the autophagosome | - | - | [129] |
| Palmitoyl moeity | TLRs | Innate immune response, regulation of immune receptor functions | - | - | [129,228] |
| Several lipid moieties | Several proteins | Plasmodium falciparum (malaria) | - | NMT validated as an attractive antimalarial drug target | [129] |
| Several lipid moieties | Several proteins | Trypanosoma brucei (human African trypanosomiasis) | - | NMT identified as a promising target for sleeping sickness (inhibitor DDD85646) | [129] |
| Fatty acylation | Rho-family GTPases (lysine residues) | Vibrio cholera | Toxin peptide catalyzing the fatty acylation of lysine residues of Rho-family GTPases | - | [229] |
| Chol | CR3 and others | Mycobacterium tuberculosis | Extractable lipids they are important virulence factors | Host Chol is required for receptor-mediated phagocytosis of M. tuberculosis by a macrophage. Blocking antibodies showed that Chol is required for mycobacterial entry via CR3. Statins showed promise in vitro and in vivo for the treatment of tuberculosis |
[230] |
| Diverse lipid moieties | Several proteins | Herpes simplex virus | - | - | [129] |
| Lipid rafts | CD4 | HIV infection | PUFAs, increased amount of lipid rafts | Disruption of host cell lipid rafts with cyclodextrin prevents HIV infection. Inhibiting sphingolipid synthesis by the virus particle reduces its infective capacity. | [185] |
| Myristoylation | Gag protein | HIV infection | Targeting lipidated viral or host proteins may lead to new antiviral agents. | [129,230] | |
| Chol | Gp41 fusion protein | HIV infection | - | - | [129,230] |
| Phosphoinositides | - | HIV infection | Effect on positive membrane curvature | - | [230] |
| Lipid rafts, edges of Chol-rich domains | CD4-CCR5/CXCR4 | HIV infection | Effect on the budding out of the host cell | - | [230] |
| Diverse lipid components | Gag-Gag, GPCR | HIV infection | Effect on the budding out of the host cell | - | [230] |
| Diverse lipid components | Gag multimerization | HIV infection | Budding virus are enriched in several lipids compared to the plasma membrane composition of the infected cells from which they originate | - | [230] |
Abbreviations: AP-1, activator protein 1; Atg8, autophagy-related protein 8; CCR5, C-C chemokine receptor type 5; CD3, cluster of differentiation 3; CD4, cluster of differentiation 4; CD45, cluster of differentiation 45; CR3, complement receptor 3; CXCR4, C-X-C chemokine receptor type 4; FcR, Fc receptor; IL-2, interleukin 2; LC3, light chain 3; LCK, lymphocyte-specific protein tyrosine kinase; NF-kB, nuclear factor kB; NMT, N-myristoyltransferase; PKC, protein kinase C; PTKs, tyrosine-protein kinase; SLE, Systemic lupus erythematosus; TLR, Toll-like receptors; HIV, Human Immunodeficiency Virus.