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Interleukin 13-Induced Inflammation Increases DPP4 Abundance but Does Not Enhance Middle East Respiratory Syndrome

Kun Li1, Jennifer A Bartlett1, Christine L Wohlford-Lenane1

  • 1Department of Pediatrics, Pappajohn Biomedical Institute, Carver College of Medicine, University of Iowa, Iowa City, IA.

The Journal of Infectious Diseases
|September 12, 2023
PubMed
Abstract

Insights

Individuals with chronic lung conditions like asthma may not be more susceptible to Middle East respiratory syndrome coronavirus (MERS-CoV) due to increased DPP4 receptor levels. Other factors likely influence MERS-CoV infection severity.

Area of Science:

  • Virology
  • Immunology
  • Pulmonology

Background:

  • Chronic pulmonary conditions, including asthma and COPD, elevate MERS-CoV morbidity and mortality risks.
  • Increased expression of the MERS-CoV receptor, dipeptidyl peptidase 4 (DPP4), was hypothesized as a cause for heightened susceptibility.

Purpose of the Study:

  • To investigate the impact of Th2 inflammation, mimicking chronic airway disease, on DPP4 expression and MERS-CoV susceptibility.
  • To determine if elevated DPP4 levels in airway epithelia influence MERS-CoV entry and replication.

Main Methods:

  • Primary human airway epithelia were treated with the Th2 cytokine IL-13 to model chronic airway disease.
  • DPP4 protein levels, MERS-CoV entry, and replication were assessed following IL-13 exposure.
  • Goblet cell metaplasia and transcriptional changes were analyzed.

Main Results:

  • Short-term (3-day) IL-13 exposure increased DPP4 protein abundance.
  • Long-term (21-day) IL-13 treatment elevated DPP4 levels and induced goblet cell metaplasia.
  • Despite increased DPP4, MERS-CoV entry and replication were not significantly affected by IL-13 treatment.

Conclusions:

  • Elevated DPP4 levels alone do not appear to be the primary driver of increased MERS severity in Th2-inflamed airways.
  • IL-13 significantly alters gene expression in airway epithelia, impacting innate immunity and antiviral responses.
  • Complex interactions between DPP4 abundance and other factors likely dictate MERS-CoV infection outcomes.
Keywords:
DPP4IL-13MERS-CoVairway epitheliath2 inflammation

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