Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Comorbid diabetes results in immune dysregulation and enhanced disease severity following MERS-CoV infection
Kirsten A. Kulcsar, … , Sarah E. Beck, Matthew B. Frieman
Kirsten A. Kulcsar, … , Sarah E. Beck, Matthew B. Frieman
Published September 24, 2019
Citation Information: JCI Insight. 2019;4(20):e131774. https://doi.org/10.1172/jci.insight.131774.
View: Text | PDF
Research Article Infectious disease Virology

Comorbid diabetes results in immune dysregulation and enhanced disease severity following MERS-CoV infection

  • Text
  • PDF
Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 in Saudi Arabia and has caused over 2400 cases and more than 800 deaths. Epidemiological studies identified diabetes as the primary comorbidity associated with severe or lethal MERS-CoV infection. Understanding how diabetes affects MERS is important because of the global burden of diabetes and pandemic potential of MERS-CoV. We used a model in which mice were made susceptible to MERS-CoV by expressing human DPP4, and type 2 diabetes was induced by administering a high-fat diet. Upon infection with MERS-CoV, diabetic mice had a prolonged phase of severe disease and delayed recovery that was independent of virus titers. Histological analysis revealed that diabetic mice had delayed inflammation, which was then prolonged through 21 days after infection. Diabetic mice had fewer inflammatory monocyte/macrophages and CD4+ T cells, which correlated with lower levels of Ccl2 and Cxcl10 expression. Diabetic mice also had lower levels of Tnfa, Il6, Il12b, and Arg1 expression and higher levels of Il17a expression. These data suggest that the increased disease severity observed in individuals with MERS and comorbid type 2 diabetes is likely due to a dysregulated immune response, which results in more severe and prolonged lung pathology.

Authors

Kirsten A. Kulcsar, Christopher M. Coleman, Sarah E. Beck, Matthew B. Frieman

×

Figure 6

Cytokine and chemokine gene expression in the lungs is altered in male diabetic DPP4H/M mice following MERS-CoV infection.

Options: View larger image (or click on image) Download as PowerPoint
Cytokine and chemokine gene expression in the lungs is altered in male d...
Male diabetic and control DPP4H/M mice were infected intranasally with 1.5e5 PFU of MERS-CoV Jordan. Lung tissue was collected at days 2, 4, 7, 10, 14, and 21 after infection and from PBS-infected mice and was homogenized in TRIzol. RNA was isolated, cDNA was synthesized, and gene expression was determined using quantitative PCR. Gene expression was normalized to GAPDH, and fold change was calculated relative to PBS infected mice. Gene expression was determined for (A) Ccl2, (B) Tnfa, (C) Il6, (D) Il12b, (E) Nos2, (F) Arg1, (G) Cxcl10, (H) Il4, (I) Ifng, (J) Il17a, (K) Foxp3, and (L) Il10. Data are pooled from 2 to 3 independent experiments with n = 3–16 mice/group and are presented as the mean ± SEM. *P < 0.05; **P < 0.01; and ***P < 0.001 as determined by 2-way ANOVA with Holm-Šídák posttest.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts