Abstract
Glycerol monolaurate (GML) is a monoglyceride with well characterized anti-microbial properties. Because of these properties, GML is widely used in food, cosmetics, and personal care products and currently being tested as a therapeutic for menstrual associated toxic shock syndrome, superficial wound infections, and HIV transmission. Recently, we have described that GML potently suppresses select T cell receptor (TCR)-induced signaling events, leading to reduced human T cell effector functions. However, how soluble host factors present in the blood and at sites of infection affect GML-mediated human T cell suppression is unknown. In this study, we have characterized how human serum albumin (HSA) affects GML-induced inhibition of human T cells. We found that HSA and other serum albumins bind to 12 carbon acyl side chain of GML at low micromolar affinities and restores the TCR-induced formation of LAT, PLC-γ1, and AKT microclusters at the plasma membrane. Additionally, HSA reverses GML mediated inhibition of AKT phosphorylation and partially restores cytokine production in GML treated cells. Our data reveal that HSA, one of the most abundant proteins in the human serum and at sites of infections, potently reverses the suppression of human T cells by GML. This suggests that GML-driven human T cell suppression depends upon the local tissue environment, with albumin concentration being a major determinant of GML function.
Highlights
Glycerol monolaurate (GML) is composed of a glycerol head group with one fully saturated 12-carbon medium chain fatty acid
human serum albumin (HSA) allows the formation of AKT, LAT, and PLC-γ1 microclusters, restores AKT phosphorylation at threonine 308 and serine 473, and rescues IFN-γ, IL-2, IL-10, and TNFα production in GML-treated cells. These results show that the degree of T cell suppression by GML is inversely correlated with the HSA concentration
HSA potentially binds to GML, a fatty acid monoester, and alters the ability of GML to inhibit human T cell function
Summary
Glycerol monolaurate (GML) is composed of a glycerol head group with one fully saturated 12-carbon medium chain fatty acid. GML potently suppresses the growth of a wide spectrum of pathogens, including gram positive and negative bacteria, fungi, and enveloped viruses [1,2,3,4,5,6]. Due to these antimicrobial properties, GML is incorporated in numerous commercial products such as deodorants, lotions, cosmetics, foods, and homeopathic supplements [7,8,9]. The commercial and clinical use of GML is greatly expanding. The antimicrobial properties of GML may act at sites distal to the administered site. Rodents orally fed with GML have reduced Staphylococcus Aureus induced peritonitis
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