Susceptibility of Human Pancreatic beta Cells for Cytomegalovirus Infection and the Effects on Cellular Immunogenicity

M.J. Smelt, M.M. Faas, Bart de Haan, C. Draijer, G.C.G. Hugenholtz, A. de Haan, M.A. Engelse, E.J.P. de Koning, P. de Vos

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Samenvatting

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 beta 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 beta 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 beta cells was determined.

Results: beta 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 beta-cell HCMV infection and infection-enhanced cellular immunogenicity may have important consequences for native or transplanted beta-cell survival.

Originele taal-2English
Pagina's (van-tot)39-49
Aantal pagina's11
TijdschriftPANCREAS
Volume41
Nummer van het tijdschrift1
DOI's
StatusPublished - jan-2012

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