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

Fingerprint

Cytomegalovirus Infections
Cytomegalovirus
Infection
Cytokines
Blood Cells
CD58 Antigens
Insulinoma
Viral Proteins
Intercellular Adhesion Molecule-1
Major Histocompatibility Complex
Type 1 Diabetes Mellitus
Allografts
Immune System
Cell Survival
Cell Death
Ligands

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

Cite this

Smelt, M. J., Faas, M. M., de Haan, B. J., Draijer, C., Hugenholtz, G. C. G., de Haan, A., ... 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
Smelt, Maaike J ; Faas, Marijke M ; de Haan, Bart J ; Draijer, Christina ; Hugenholtz, Greg C G ; de Haan, Aalzen ; Engelse, Marten A ; de Koning, Eelco J P ; de Vos, Paul. / Susceptibility of human pancreatic β cells for cytomegalovirus infection and the effects on cellular immunogenicity. In: Pancreas. 2012 ; Vol. 41, No. 1. pp. 39-49.
@article{516ffc401afa44589dfab2749aadd585,
title = "Susceptibility of human pancreatic β cells for cytomegalovirus infection and the effects on cellular immunogenicity",
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 {\circledC} 2012 by Lippincott Williams & Wilkins.",
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",
author = "Smelt, {Maaike J} and Faas, {Marijke M} and {de Haan}, {Bart J} and Christina Draijer and Hugenholtz, {Greg C G} and {de Haan}, Aalzen and Engelse, {Marten A} and {de Koning}, {Eelco J P} and {de Vos}, Paul",
year = "2012",
month = "1",
doi = "10.1097/MPA.0b013e31821fc90c",
language = "English",
volume = "41",
pages = "39--49",
journal = "Pancreas",
issn = "0885-3177",
publisher = "Lippincott Williams & Wilkins",
number = "1",

}

Smelt, MJ, Faas, MM, de Haan, BJ, Draijer, C, Hugenholtz, GCG, de Haan, A, Engelse, MA, de Koning, EJP & de Vos, P 2012, 'Susceptibility of human pancreatic β cells for cytomegalovirus infection and the effects on cellular immunogenicity', Pancreas, vol. 41, no. 1, pp. 39-49. https://doi.org/10.1097/MPA.0b013e31821fc90c

Susceptibility of human pancreatic β cells for cytomegalovirus infection and the effects on cellular immunogenicity. / Smelt, Maaike J; Faas, Marijke M; de Haan, Bart J; Draijer, Christina; Hugenholtz, Greg C G; de Haan, Aalzen; Engelse, Marten A; de Koning, Eelco J P; de Vos, Paul.

In: Pancreas, Vol. 41, No. 1, 01.2012, p. 39-49.

Research output: Contribution to journalArticleAcademicpeer-review

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

Y1 - 2012/1

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 -