title: Glycerol Monolaurate (GML) inhibits human T cell signaling and function by disrupting lipid dynamics.
abstract: Glycerol Monolaurate (GML) is a naturally occurring fatty acid widely utilized in food, cosmetics, and homeopathic supplements. GML is a potent antimicrobial agent that targets a range of bacteria, fungi, and enveloped viruses but select findings suggest that GML also has immunomodulatory functions. In this study, we have mechanistically examined if GML affects the signaling and functional output of human primary T cells. We found that GML potently altered order and disorder dynamics in the plasma membrane that resulted in reduced formation of LAT, PLC-γ, and AKT microclusters. Altered membrane events induced selective inhibition of TCR-induced phosphorylation of regulatory P85 subunit of PI3K and AKT as well as abrogated calcium influx. Ultimately, GML treatment potently reduced TCR-induced production of IL-2, IFN-γ, TNF-α, and IL-10. Our data reveal that the widely used anti-microbial agent GML also alters the lipid dynamics of human T cells, leading to their defective signaling and function.
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, United States.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, United States.
authors.forename: Aline
authors.initials: A
authors.lastname: Sandouk
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, United States.
authors.forename: Jon C D
authors.initials: JC
authors.lastname: Houtman
mesh_terms: D018106:CD28 Antigens / Q000037:antagonists & inhibitors / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007848:Laurates / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects*; D050178:Monoglycerides / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018106:CD28 Antigens; D016207:Cytokines; D007848:Laurates; D050178:Monoglycerides; D011948:Receptors, Antigen, T-Cell; C020777:monolaurin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051966:Phospholipase C gamma; D002118:Calcium