Rxivist logo

Hypercapnia Suppresses Macrophage Antiviral Activity and Increases Mortality of Influenza A 1 Infection via Akt1

By S. Marina Casalino-Matsuda, Fei Chen, Francisco J. Gonzalez-Gonzalez, Aisha Nair, Sandra Dib, Alex Yemelyanov, Khalilah Gates, G.R. Scott Budinger, Greg J. Beitel, Peter H. S. Sporn

Posted 14 Feb 2020
bioRxiv DOI: 10.1101/2020.02.13.946400 (published DOI: 10.4049/jimmunol.2000085)

Hypercapnia, elevation of the partial pressure of CO2 in blood and tissues, is a risk factor for mortality in patients with severe acute and chronic lung diseases. We previously showed that hypercapnia inhibits multiple macrophage and neutrophil antimicrobial functions, and that it increases the mortality of bacterial pneumonia in mice. Here, we show that normoxic hypercapnia increases viral replication, lung injury and mortality in mice infected with influenza A virus (IAV). Elevated CO2 increased IAV replication and inhibited antiviral gene and protein expression in macrophages in vivo and in vitro. Hypercapnia potentiated IAV-induced activation of Akt, while specific pharmacologic inhibition or shRNA knockdown of Akt1 in alveolar macrophages blocked hypercapnia′s effects on IAV growth and the macrophage antiviral response. Our findings suggest that targeting Akt1 or downstream pathways through which elevated CO2 signals could enhance macrophage antiviral host defense and improve clinical outcomes in hypercapnic patients with advanced lung disease.

Download data

  • Downloaded 163 times
  • Download rankings, all-time:
    • Site-wide: 76,048 out of 89,956
    • In immunology: 2,130 out of 2,607
  • Year to date:
    • Site-wide: 22,443 out of 89,956
  • Since beginning of last month:
    • Site-wide: 50,491 out of 89,956

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)