TY - JOUR
T1 - Susceptibility of human pancreatic β cells for cytomegalovirus infection and the effects on cellular immunogenicity
AU - Smelt, Maaike J
AU - Faas, Marijke M
AU - de Haan, Bart J
AU - Draijer, Christina
AU - Hugenholtz, Greg C G
AU - de Haan, Aalzen
AU - Engelse, Marten A
AU - de Koning, Eelco J P
AU - de Vos, Paul
PY - 2012/1/1
Y1 - 2012/1/1
N2 - 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.
AB - 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.
KW - CD58 Antigens/immunology
KW - Cadaver
KW - Cell Line, Tumor
KW - Cell Survival/immunology
KW - Cells, Cultured
KW - Cytokines/immunology
KW - Cytomegalovirus/genetics
KW - Cytomegalovirus Infections/virology
KW - Fibroblasts/immunology
KW - Flow Cytometry
KW - Histocompatibility Antigens Class I/immunology
KW - Host-Pathogen Interactions/immunology
KW - Humans
KW - Immunity/immunology
KW - Insulin-Secreting Cells/immunology
KW - Insulinoma/immunology
KW - Intercellular Adhesion Molecule-1/immunology
KW - Leukocytes, Mononuclear/cytology
KW - Receptors, Chemokine/genetics
KW - Species Specificity
KW - Viral Proteins/genetics
KW - Virus Replication/genetics
UR - http://www.mendeley.com/research/susceptibility-human-pancreatic-%CE%B2-cells-cytomegalovirus-infection-effects-cellular-immunogenicity
U2 - 10.1097/MPA.0b013e31821fc90c
DO - 10.1097/MPA.0b013e31821fc90c
M3 - Article
C2 - 22158077
VL - 41
SP - 39
EP - 49
JO - Pancreas
JF - Pancreas
SN - 0885-3177
IS - 1
ER -