Host Defense and Parasite Evasion
Eric S. Loker, Bruce V. Hofkin in Parasitology, 2015
These examples feature parasites that normally infect APCs. Plasmodium falciparum, of course, first targets hepatocytes and then erythrocytes for intracellular replication. Yet since the late 1990s, it has been known that infected erythrocytes can somehow reduce MHC II expression on dendritic cells. Such dendritic cells also secrete an altered cytokine profile, which, as we will see shortly, results in a less protective adaptive immune response. It has subsequently been found that infected erythrocytes express a parasite-encoded protein, called Plasmodium falciparum erythrocyte membrane protein 1 (PfEMPl), on their surfaces. This protein serves as a ligand for CD36, found on the surface of dendritic cells. Such binding initiates an intracellular signal that inhibits MHC II expression. The clinical significance of this is suggested by the observation that patients with either severe or mild malaria have reduced MHC II expression on dendritic cells as compared to healthy controls. Paradoxically, it has been observed that infected red blood cells with high CD36 binding affinity are more frequently observed in patients with mild rather than severe malaria. This difference may result from the reduced expression of pro-inflammatory cytokines in response to the parasite that exacerbate the symptoms of disease.
Host Defense and Parasite Evasion
Eric S. Loker, Bruce V. Hofkin in Parasitology, 2023
These examples feature parasites that normally infect APCs. P. falciparum, of course, first targets hepatocytes and then erythrocytes for intracellular replication. Yet since the late 1990s, it has been known that infected erythrocytes can somehow reduce MHC II expression on dendritic cells. Such dendritic cells also secrete an altered cytokine profile, which, as we will see shortly, results in a less protective adaptive immune response. As discussed in Chapter 3 (see p. 119), infected erythrocytes express erythrocyte membrane protein 1 (PfEMPl), on their surfaces. This protein serves as a ligand for CD36, found on the surface of dendritic cells. Such binding initiates an intracellular signal that inhibits MHC II expression. The clinical significance of this is suggested by the observation that patients with either severe or mild malaria have reduced MHC II expression on dendritic cells as compared to healthy controls.
Heterogeneity Among CD36+ Cells in Normal and Diseased Human Skin
Brian J. Nickoloff in Dermal Immune System, 2019
The CD36 antigen is differentially expressed on a heterogeneous population of cells in normal and diseased human skin, e.g., dermal macrophages, endothelial cells, keratinocytes, melanocytes, and occasionally epidermal LCs/macrophages. Little is known about the exact function of this molecule or the factor(s) which regulate its expression, with the notable exception that IFN-γ seems to be capable of inducing and upregulating CD36 antigen expression on KCs128 and endothelial cells,83 respectively. With regard to the cutaneous immune system, some of the most relevant data suggest that CD36+/HLA-DR+ macrophages in the skin39,92 are phenotypically analogous to peripheral blood OKM1−/OKM5+ monocytes.34 Moreover, they are functionally similar in that CD36+/HLA-DR+ skin-derived leukocytes are capable of inducing autologous TC proliferation, display phagocytic activity, and have the ability to present alloantigens, soluble antigens, as well as mitogens.39,92 There also is evidence that CD36 may function as a signal-transducing molecule in monocytes since anti-CD36 F(ab’)2 directly induced an oxidative burst in these cells, as determined by chemiluminescence.129
CD36 as a target for metabolic modulation therapy in cardiac disease
Published in Expert Opinion on Therapeutic Targets, 2021
Jan F.C. Glatz, Fang Wang, Miranda Nabben, Joost J.F.P. Luiken
Of major importance is the specificity of the approach to alter CD36 functioning. First, CD36 is a scavenger receptor with a broad cell-type expression, being found not only in cardiac and skeletal myocytes, but also in adipocytes, intestinal enterocytes, macrophages, and monocytes, while its expression in the liver is induced upon high fat consumption [50]. Second, CD36 not only binds long-chain fatty acids, but also is a receptor for oxidized low-density lipoproteins, thrombospondin, and collagen, apoptotic cells, and erythrocytes infected with Plasmodium falciparum [reviewed in 50]. As a result, CD36 is a multifunctional protein involved in a variety of (mostly lipid-related) pathways. Therefore, when altering CD36 presence or functioning by direct inhibition of the protein, the possibility of introducing unwanted side effects should always be considered and evaluated. For instance, it has been found that blocking CD36 inhibits macrophage phagocytosis of dead myocytes and neutrophils resulting in impaired removal of debris and adverse left ventricular remodeling post-myocardial infarction [51]. However, this limitation may be overcome by indirect approaches to alter CD36 presence in the plasma membrane, i.e. by targeting the subcellular recycling of CD36 between endosomes and the plasma membrane, and do so in a tissue-specific manner [52] as explained below.
Cardioprotective effect of β-d -mannuronic acid (M2000) as a novel NSAID on gene expression of oxLDL scavenger receptors in the experimental diabetic model
Published in Immunopharmacology and Immunotoxicology, 2018
Seyed Shahabeddin Mortazavi-Jahromi, Shahab Alizadeh, Mohammad Hassan Javanbakht, Abbas Mirshafiey
Ganjifrockwala et al. reported a higher level of oxLDL in diabetic patients compared with non-diabetics [29]. After activating the NF-κb signaling pathway, the oxLDL increases the production of proinflammatory cytokines in human dendritic cells, contributing to their maturation and differentiation [30]. Lu et al. indicated that diabetes-induced hyperglycemia increases oxLDL uptake by dendritic cells and thus potentially contributes to the development and exacerbation of atherosclerosis [31]. Ye et al. showed that SR-A is a major receptor for oxLDL uptake by mesenchymal stem cells whose expression is increased through exposure to oxLDL [32]. Handberg et al. for the first time illustrated that the soluble CD36 levels are increased in diabetic samples. The soluble CD36 is strongly associated with atherosclerosis risk factors such as insulin resistance and glycemic control. It has been reported that the CD36 is able to predict the atherosclerosis process in diabetic patients [33]. It has been revealed in two separate studies that diabetes-induced hyperglycemia increases LOX-1 gene expression and differentiates foam cells into macrophages, leading to diabetes-induced atherosclerosis [14,34]. Yoshida et al. reported that oxLDL could increase scavenger receptor expressions (SR-A, CD36, CD68) in rat peritoneal macrophages [35].
A complete proteomic profile of human and bovine milk exosomes by liquid chromatography mass spectrometry
Published in Expert Review of Proteomics, 2021
Kanchan Manohar Vaswani, Hassendrini Peiris, Yong Qin Koh, Rebecca J. Hill, Tracy Harb, Buddhika J. Arachchige, Jayden Logan, Sarah Reed, Peter S. W. Davies, Murray D. Mitchell
Both the human and bovine milk exosomes contained Platelet glycoprotein four in the top 20 abundant list. This protein, also called CD36, is involved in pathogen recognition, phagocytosis, and pathogen-induced signaling [32] and is a receptor for a range of ligands (such as TLR4 and hence LPS recognition). The formation of CD36 ligand-binding complexes promotes signal transduction and internalization into cells. Since exosomes have been identified as novel signal transducers, this can be explored further since within cells CD36 responses have been shown to play roles in angiogenesis, inflammatory responses, fatty acid metabolism, taste, and dietary fat processing in the intestine, participating in muscle lipid utilization, adipose energy storage, and gut fat absorption and may also serve as a therapeutic target for reducing the postprandial hypertriglyceridemia linked to cardiovascular issues [33–35]. Wilcox C.P. et al. report that there is a form of CD36 that is distinct from the type found in MFGM [36]. Since CD36 is found within the MFGM as well as in the exosomes of both human and bovine milk, it will be important to study further how similar or different its function is compared to its function in cells. Garcia et al. 2019 identified that the CD36 in circulating exosomes increased postprandially [37] which is interesting as studies need to confirm if this is the case after infants ingest different types of milk.
Related Knowledge Centers
- Cluster of Differentiation
- Collagen
- Integral Membrane Protein
- Ligand
- Protein
- Red Blood Cell
- Cluster of Differentiation
- Gene
- Scavenger Receptor
- Cell
- Thrombospondin