Effect of elevated carbon dioxide on bronchial epithelial innate immune receptor response to organic dust from swine confinement barns

• Immune responses to barn dust respond differently to hypercapnic conditions than individual TLR ligands.
• We show here an anti-inflammatory response of hypercapnia in a bronchial epithelial cell line to LPS and PAM3CSK.
• We show a pro-inflammatory response to organic barn dust in a bronchial epithelial cell line.
• Increasing IL-8 and MCP-1 levels may be a response to strong pro-inflammatory signals from many sources.

Hypercapnia is known to have immunoregulatory effects within the lung. Cell culture systems demonstrate this in both macrophages and alveolar cell lines, suggesting that the alveoli are affected by changes in CO2 levels. We hypothesized that hypercapnia would also modulate human bronchial epithelial cell immune responses. Innate immune responses to Pam3CSK4 (TLR2 ligand), LPS (TLR4 ligand) and a complex innate immune stimulus, an extract from the organic dust of swine confinement barns (barn dust extract or BDE), were tested in a human bronchial epithelial cell line, BEAS-2B. Both TLR ligands showed a decrease in IL-6 and IL-8 production, and an increase in MCP-1 in response to elevated CO2 indicating an enhancement in cytokine production to hypercapnia. This change was not reflected in expression levels of TLR receptor RNA which remained unchanged in response to elevated CO2. Interestingly, barn dust showed an increase in IL-6, IL-8 and MCP-1 response at 9% CO2, suggesting that elevated CO2 exerts different effects on different stimuli. Our results show that airway epithelial cell immune responses to barn dust respond differently to hypercapnic conditions than individual TLR ligands.