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Exosomes released from mycoplasma infected tumor cells activate inhibitory B cells

Yang, C and Chalasani, G and Ng, YH and Robbins, PD (2012) Exosomes released from mycoplasma infected tumor cells activate inhibitory B cells. PLoS ONE, 7 (4).

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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. © 2012 Yang et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Yang, C
Chalasani, Ggec12@pitt.eduGEC12
Ng, YH
Robbins, PDprobb@pitt.eduPROBB
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorCámara, Niels Olsen SaraivaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 27 April 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 4
DOI or Unique Handle: 10.1371/journal.pone.0036138
Schools and Programs: School of Medicine > Immunology
School of Medicine > Microbiology and Molecular Genetics
Refereed: Yes
MeSH Headings: Animals; Antigens, CD3--metabolism; B-Lymphocytes--immunology; Cell Line, Tumor; Cell Proliferation; Coculture Techniques; Cytokines--biosynthesis; Exosomes--metabolism; Exosomes--ultrastructure; Extracellular Signal-Regulated MAP Kinases--metabolism; Humans; Intracellular Membranes--metabolism; Intracellular Space--metabolism; Lymphocyte Activation--immunology; Mice; Mycoplasma--metabolism; Mycoplasma Infections--immunology; Phosphorylation--drug effects; Receptors, Antigen, T-Cell--immunology; Signal Transduction--immunology; Spleen--cytology; Spleen--metabolism; Staining and Labeling; T-Lymphocytes--immunology
Other ID: NLM PMC3338602
PubMed Central ID: PMC3338602
PubMed ID: 22558358
Date Deposited: 24 Sep 2012 20:21
Last Modified: 26 Jan 2019 16:55
URI: http://d-scholarship.pitt.edu/id/eprint/14177

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