Influenza A virus elevates active cathepsin B in primary murine DC

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Dendritic cells (DCs) are crucial for pathogen recognition and initiating adaptive immunity.
• Influenza A virus infection activates DCs, leading to viral peptide presentation on MHC class II molecules.
• Previous studies show persistent DC activation after influenza infection, but effects on antigen processing machinery were unknown.

Purpose of the Study:

• To investigate the long-term effects of influenza A virus on the endo/lysosomal antigen-processing machinery of DCs.
• To determine if influenza A virus impacts cathepsin activity and its role in antigen presentation.

Main Methods:

• Mice infected with influenza A virus (A/HKx31).
• Analysis of lung, splenic, and bone marrow-derived DCs.
• Measurement of cathepsin B and X levels and activity.
• In vitro experiments using UV-inactivated influenza A virus and cathepsin inhibitors.

Main Results:

• Influenza-exposed DCs showed increased T cell stimulation from intact protein antigens, indicating enhanced processing.
• Cathepsin B levels and activity were significantly upregulated in lung DCs 30 days post-infection.
• Both in vivo and in vitro influenza exposure increased Cathepsin B activity in DCs.
• Cathepsin activity was essential for generating T cell epitopes from intact ovalbumin.

Conclusions:

• Influenza A virus infection has lasting effects on DC antigen processing capabilities.
• The study identifies cathepsin B as a key enzyme upregulated by influenza, enhancing antigen processing.
• These findings highlight the impact of influenza on the MHC class II antigen-processing pathway, vital for CD4(+) T cell activation.