Human Metapneumovirus Infection Inhibits Cathelicidin Antimicrobial Peptide Expression in Human Macrophages

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Human cathelicidin antimicrobial peptide (CAMP) is vital for innate immunity, possessing antimicrobial and immunomodulatory roles.
• Pathogen-induced downregulation of CAMP is known, but its modulation during viral infections remains largely uncharacterized.

Purpose of the Study:

• To investigate the effect of human metapneumovirus (hMPV) infection on CAMP expression in human macrophages.
• To elucidate the underlying mechanisms of hMPV-mediated CAMP suppression.

Main Methods:

• Human macrophages were infected with hMPV to assess CAMP expression.
• Analysis of vitamin D and interferon signaling pathways.
• Investigated the role of C/EBPα transcription factor using knockdown studies.
• Explored TLR1/2 ligand treatment effects on CAMP and C/EBPα.

Main Results:

• hMPV infection significantly suppressed both basal and vitamin D-induced CAMP expression in human macrophages.
• The suppression was independent of vitamin D and interferon signaling pathways.
• hMPV infection repressed C/EBPα expression, which was identified as critical for CAMP expression.
• TLR1/2 ligand treatment mimicked hMPV's effect, suggesting a common regulatory mechanism via C/EBPα.

Conclusions:

• hMPV infection downregulates CAMP expression in macrophages through a vitamin D- and interferon-independent mechanism.
• C/EBPα is a key mediator of hMPV-induced suppression of CAMP.
• Pathogen-mediated downregulation of CAMP may involve C/EBPα, impacting host antimicrobial responses.