tetano
Editor, Senior Moderator
J Infect Dis
. 2023 Sep 12;jiad383.
doi: 10.1093/infdis/jiad383. Online ahead of print. IL-13 induced inflammation increases DPP4 abundance but does not enhance MERS-CoV replication in airway epithelia
Kun Li[SUP] 1 [/SUP], Jennifer A Bartlett[SUP] 1 [/SUP], Christine L Wohlford-Lenane[SUP] 1 [/SUP], Biyun Xue[SUP] 2 [/SUP], Andrew L Thurman[SUP] 2 [/SUP], Thomas M Gallagher[SUP] 3 [/SUP], Alejandro A Pezzulo[SUP] 2 [/SUP], Paul B McCray[SUP] 1 4 [/SUP]
Affiliations
Background: Chronic pulmonary conditions such as asthma and COPD increase the risk of morbidity and mortality during infection with the Middle East respiratory syndrome coronavirus (MERS-CoV). We hypothesized that individuals with such comorbidities are more susceptible to MERS-CoV infection due to increased expression of its receptor, dipeptidyl peptidase 4 (DPP4).
Methods: We modeled chronic airway disease by treating primary human airway epithelia with the Th2 cytokine IL-13, examining how this impacted DPP4 protein levels along with MERS-CoV entry and replication.
Results: IL-13 exposure for 3 days led to increased DPP4 protein abundance, while a 21-day treatment increased DPP4 levels and caused goblet cell metaplasia. Surprisingly, despite this increase in receptor availability, MERS-CoV entry and replication were not significantly impacted by IL-13 treatment.
Conclusions: Our results suggest that increased DPP4 abundance is likely not the primary mechanism leading to increased MERS severity in the setting of Th2 inflammation. Transcriptional profiling analysis highlighted the complexity of IL-13 induced changes in airway epithelia, including altered expression of genes involved in innate immunity, antiviral responses, and maintenance of the extracellular mucus barrier. These data suggest that additional factors likely interact with DPP4 abundance to determine MERS-CoV infection outcomes.
Keywords: DPP4; IL-13; MERS-CoV; Middle East respiratory syndrome; Th2 inflammation; airway epithelia; asthma; coronavirus; goblet cell metaplasia.
. 2023 Sep 12;jiad383.
doi: 10.1093/infdis/jiad383. Online ahead of print. IL-13 induced inflammation increases DPP4 abundance but does not enhance MERS-CoV replication in airway epithelia
Kun Li[SUP] 1 [/SUP], Jennifer A Bartlett[SUP] 1 [/SUP], Christine L Wohlford-Lenane[SUP] 1 [/SUP], Biyun Xue[SUP] 2 [/SUP], Andrew L Thurman[SUP] 2 [/SUP], Thomas M Gallagher[SUP] 3 [/SUP], Alejandro A Pezzulo[SUP] 2 [/SUP], Paul B McCray[SUP] 1 4 [/SUP]
Affiliations
- PMID: 37698016
- DOI: 10.1093/infdis/jiad383
Background: Chronic pulmonary conditions such as asthma and COPD increase the risk of morbidity and mortality during infection with the Middle East respiratory syndrome coronavirus (MERS-CoV). We hypothesized that individuals with such comorbidities are more susceptible to MERS-CoV infection due to increased expression of its receptor, dipeptidyl peptidase 4 (DPP4).
Methods: We modeled chronic airway disease by treating primary human airway epithelia with the Th2 cytokine IL-13, examining how this impacted DPP4 protein levels along with MERS-CoV entry and replication.
Results: IL-13 exposure for 3 days led to increased DPP4 protein abundance, while a 21-day treatment increased DPP4 levels and caused goblet cell metaplasia. Surprisingly, despite this increase in receptor availability, MERS-CoV entry and replication were not significantly impacted by IL-13 treatment.
Conclusions: Our results suggest that increased DPP4 abundance is likely not the primary mechanism leading to increased MERS severity in the setting of Th2 inflammation. Transcriptional profiling analysis highlighted the complexity of IL-13 induced changes in airway epithelia, including altered expression of genes involved in innate immunity, antiviral responses, and maintenance of the extracellular mucus barrier. These data suggest that additional factors likely interact with DPP4 abundance to determine MERS-CoV infection outcomes.
Keywords: DPP4; IL-13; MERS-CoV; Middle East respiratory syndrome; Th2 inflammation; airway epithelia; asthma; coronavirus; goblet cell metaplasia.