title: Exosomes released from Mycoplasma infected tumor cells activate inhibitory B cells.
abstract: Mycoplasmas cause numerous human diseases and are common opportunistic pathogens in cancer patients and immunocompromised individuals. Mycoplasma infection elicits various host immune responses. Here we demonstrate that mycoplasma-infected tumor cells release exosomes (myco+ exosomes) that specifically activate splenic B cells and induce splenocytes cytokine production. Induction of cytokines, including the proinflammatory IFN-γ and the anti-inflammatory IL-10, was largely dependent on the presence of B cells. B cells were the major IL-10 producers. In splenocytes from B cell deficient μMT mice, induction of IFN-γ+ T cells by myco+ exosomes was greatly increased compared with wild type splenocytes. In addition, anti-CD3-stimulated T cell proliferation was greatly inhibited in the presence of myco+ exosome-treated B cells. Also, anti-CD3-stimulated T cell signaling was impaired by myco+ exosome treatment. Proteomic analysis identified mycoplasma proteins in exosomes that potentially contribute to the effects. Our results demonstrate that mycoplasma-infected tumor cells release exosomes carrying mycoplasma components that preferentially activate B cells, which in turn, are able to inhibit T cell activity. These results suggest that mycoplasmas infecting tumor cells can exploit the exosome pathway to disseminate their own components and modulate the activity of immune cells, in particular, activate B cells with inhibitory activity.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Chenjie
authors.initials: C
authors.lastname: Yang
authors.forename: Geetha
authors.initials: G
authors.lastname: Chalasani
authors.forename: Yue-Harn
authors.initials: YH
authors.lastname: Ng
authors.forename: Paul D
authors.initials: PD
authors.lastname: Robbins
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D017252:CD3 Complex / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D055354:Exosomes / Q000378:metabolism* / Q000648:ultrastructure; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D009174:Mycoplasma / Q000378:metabolism*; D009175:Mycoplasma Infections / Q000276:immunology*; D010766:Phosphorylation / Q000187:drug effects; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013194:Staining and Labeling; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D017252:CD3 Complex; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D048049:Extracellular Signal-Regulated MAP Kinases