title: Pseudomonas aeruginosa Quorum Sensing Molecule N-(3-Oxododecanoyl)-L-Homoserine-Lactone Induces HLA-G Expression in Human Immune Cells.
abstract: HLA-G is a nonclassical class I human leukocyte antigen (HLA) involved in mechanisms of immune tolerance. The objective of this study was to determine whether N-(3-oxododecanoyl)-l-homoserine lactone (3O-C12-HSL), a quorum sensing molecule produced by Pseudomonas aeruginosa, could modify HLA-G expression to control the host immune response. We evaluated the ability of 3O-C12-HSL to induce HLA-G expression in primary immune cells, monocytes (U937 and THP1), and T-cell lines (Jurkat) in vitro and analyzed the cellular pathway responsible for HLA-G expression. We studied the HLA-G promoter with a luciferase assay and interleukin-10 (IL-10) and p38/CREB signaling with enzyme-linked immunosorbent assay and immunofluorescence, respectively. We observed that 3O-C12-HSL is able to induce HLA-G expression in human monocytes and T cells. We showed that the induction of HLA-G by 3O-C12-HSL is p38/CREB and IL-10 dependent. 3O-C12-HSL treatment is able to arrest only the U937 cell cycle, possibly due to the peculiar expression of the ILT2 receptor in the U937 cell line. Our observations suggest HLA-G as a mechanism to create a protected niche for the bacterial reservoir, similar to the role of HLA-G molecules during viral infections.
authors.affiliation: Department of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, Ferrara, Italy.
authors.forename: Daria
authors.initials: D
authors.lastname: Bortolotti
authors.affiliation: CEA, Institute of Emerging Diseases and Innovative Therapies (iMETI), Research Division in Hematology and Immunology (SRHI), Saint-Louis Hospital, Paris, France.
authors.forename: Joel
authors.initials: J
authors.lastname: LeMaoult
authors.affiliation: Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Trapella
authors.affiliation: Department of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, Ferrara, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Di Luca
authors.affiliation: CEA, Institute of Emerging Diseases and Innovative Therapies (iMETI), Research Division in Hematology and Immunology (SRHI), Saint-Louis Hospital, Paris, France.
authors.forename: Edgardo D
authors.initials: ED
authors.lastname: Carosella
authors.affiliation: Department of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, Ferrara, Italy rbr@unife.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Rizzo
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism; D059951:HLA-G Antigens / Q000235:genetics* / Q000276:immunology; D006714:Homoserine / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D011552:Pseudomonas Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D053038:Quorum Sensing; D013601:T-Lymphocytes / Q000276:immunology; D020298:U937 Cells; D015854:Up-Regulation
chemical_list: D059951:HLA-G Antigens; C508609:IL10 protein, human; C109860:N-(3-oxododecanoyl)homoserine lactone; D016753:Interleukin-10; D006714:Homoserine; D015107:4-Butyrolactone