Susceptibility of human pancreatic β cells for cytomegalovirus infection and the effects on cellular immunogenicity

Maaike J Smelt, Marijke M Faas, Bart J de Haan, Christina Draijer, Greg C G Hugenholtz, Aalzen de Haan, Marten A Engelse, Eelco J P de Koning, Paul de Vos

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Objectives: Human cytomegalovirus (HCMV) infection has been suggested to be a causal factor in the development of type 1 diabetes, posttransplantation diabetes, and the failure of islet allografts. This effect of CMV has been interpreted as an indirect effect on the immune system rather than direct infection-induced cell death. In the present study, we investigated (i) the susceptibility of β cells to HCMV infection, (ii) regulation of immune cell-activating ligands, (iii) release of proinflammatory cytokines, and (iv) the effects on peripheral blood mononuclear cell (PBMC) activation. Methods: CM insulinoma cells and primary β cells were HCMV-infected in vitro using a laboratory and a clinical HCMV strain. The susceptibility to infection was measured by the expression of viral genes and proteins. Furthermore, expression levels of Major Histocompatibility Complex I, Intracellular Adhesion Molecule-1, and Lymphocyte Function Associated Antigen-3 and the release of proinflammatory cytokines were determined. In addition, PBMC activation to HCMV-infected β cells was determined. Results: β Cells were susceptible to HCMV infection. Moreover, the infection increased the cellular immunogenicity, as demonstrated by an increased MHC I and ICAM-1 expression and an increased proinflammatory cytokine release. Human cytomegalovirus-infected CM cells potently activated PBMCs. The infection-induced effects were dependent on both viral "sensing" and viral replication. Conclusions: In vivo β-cell HCMV infection and infection-enhanced cellular immunogenicity may have important consequences for native or transplanted β-cell survival. Copyright © 2012 by Lippincott Williams & Wilkins.
Original languageEnglish
Pages (from-to)39-49
Number of pages11
JournalPancreas
Volume41
Issue number1
DOIs
Publication statusPublished - Jan 2012
Externally publishedYes

Keywords

  • CD58 Antigens/immunology
  • Cadaver
  • Cell Line, Tumor
  • Cell Survival/immunology
  • Cells, Cultured
  • Cytokines/immunology
  • Cytomegalovirus/genetics
  • Cytomegalovirus Infections/virology
  • Fibroblasts/immunology
  • Flow Cytometry
  • Histocompatibility Antigens Class I/immunology
  • Host-Pathogen Interactions/immunology
  • Humans
  • Immunity/immunology
  • Insulin-Secreting Cells/immunology
  • Insulinoma/immunology
  • Intercellular Adhesion Molecule-1/immunology
  • Leukocytes, Mononuclear/cytology
  • Receptors, Chemokine/genetics
  • Species Specificity
  • Viral Proteins/genetics
  • Virus Replication/genetics

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  • Cite this

    Smelt, M. J., Faas, M. M., de Haan, B. J., Draijer, C., Hugenholtz, G. C. G., de Haan, A., Engelse, M. A., de Koning, E. J. P., & de Vos, P. (2012). Susceptibility of human pancreatic β cells for cytomegalovirus infection and the effects on cellular immunogenicity. Pancreas, 41(1), 39-49. https://doi.org/10.1097/MPA.0b013e31821fc90c