Myeloid Zfhx3 deficiency protects against hypercapnia-induced suppression of host defense against influenza A virus.

ABSTRACT: 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 elevated CO2 increases the mortality of bacterial and viral pneumonia in mice. Here, we show that normoxic hypercapnia downregulates innate immune and antiviral gene programs in alveolar macrophages (AMØs). We also show that zinc finger homeobox 3 (Zfhx3) - a mammalian ortholog of zfh2, which mediates hypercapnic immune suppression in Drosophila - is expressed in mouse and human macrophages. Deletion of Zfhx3 in the myeloid lineage blocked the suppressive effect of hypercapnia on immune gene expression in AMØs and d

SUBMITTER: Casalino-Matsuda SM 

PROVIDER: S-EPMC11143927 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature