Human Metapneumovirus (HMPV) Inhibits Cathelicidin Antimicrobial Peptide Expression in Human Macrophages
Nikhil Prasad Fact checked by:Thailand Medical News Team Jan 11, 2025 2 hours, 15 minutes ago
Medical News: Researchers from the Department of Clinical and Molecular Medicine at the Norwegian University of Science and Technology in Trondheim, Norway, have uncovered groundbreaking insights into how human metapneumovirus (HMPV) impacts the human immune system. Led by Youxian Li, Stine Østerhus, and Ingvild B. Johnsen, the team’s findings shed light on the virus’s ability to suppress a crucial component of the immune defense: the cathelicidin antimicrobial peptide (CAMP).
Human Metapneumovirus Inhibits Cathelicidin Antimicrobial Peptide Expression in Human Macrophages
Understanding the Human Metapneumovirus and CAMP
Human metapneumovirus is a respiratory virus first identified in 2001. It belongs to the Pneumoviridae family and is a leading cause of respiratory tract infections, particularly in young children. Meanwhile, cathelicidin antimicrobial peptide (CAMP) is a vital element of the immune system. Found in various cells, including macrophages, CAMP helps fend off bacteria, fungi, and viruses while regulating inflammation and healing wounds.
The research team sought to determine whether HMPV infection affects CAMP levels in macrophages. This
Medical News report explores how the study reveals a new layer of complexity in the interaction between pathogens and the human immune system.
Key Findings of the Study
The researchers conducted a series of experiments using human macrophages - white blood cells essential for immune defense. Their findings revealed that HMPV infection dramatically reduced both basal and vitamin D-induced expression of CAMP. Vitamin D is known to regulate CAMP levels via the vitamin D receptor (VDR) and the enzyme CYP27B1, which activates vitamin D in cells. However, the study discovered that HMPV’s suppressive effects on CAMP were independent of the vitamin D pathway.
In a surprising twist, blocking interferon signaling pathway - a critical part of the immune system’s response to viral infections - did not reverse the suppression of CAMP. This suggests that HMPV employs an interferon-independent mechanism to suppress CAMP expression.
The Role of C/EBPα in CAMP Suppression
The team pinpointed the transcription factor C/EBPα as a key player in this process. C/EBPα is essential for CAMP expression, and its levels were significantly reduced in HMPV-infected macrophages. To validate this, the researchers used RNA interference to knock down C/EBPα. The result was a corresponding decrease in CAMP expression, demonstrating that the suppression of CAMP is directly linked to the downregulation of C/EBPα.
Furthermore, they showed that treatment with toll-like receptor (TLR) ligands - molecules that simulate microbial infection - also suppressed C/EBPα and CAMP expression. This indicates a broader mechanism by which pathogens may downregulate immune responses via C/EBPα.
trong>Dependence on Viral Replication
The study also revealed that HMPV’s suppression of CAMP is dependent on active viral replication. When macrophages were exposed to UV-inactivated HMPV, which cannot replicate, the suppression of CAMP and C/EBPα was not observed. This finding underscores the active role of viral replication in modulating host immune defenses.
Implications for Immune Defense
The suppression of CAMP by HMPV could have significant implications for immune defense. CAMP not only combats pathogens directly but also helps regulate immune responses and inflammation. Its downregulation could make individuals more susceptible to secondary infections or exacerbate inflammatory conditions. These findings raise questions about how HMPV might impair broader immune system functions.
Additionally, the study highlights the complex interplay between pathogens and host defense mechanisms. By targeting C/EBPα, HMPV may be reprogramming macrophages to prioritize other immune responses, such as interferon production, over antimicrobial defenses. This “reprogramming” could represent a novel viral strategy to evade the immune system.
Potential Therapeutic Avenues
The identification of C/EBPα as a regulator of CAMP during HMPV infection opens the door to potential therapeutic interventions. Strategies that preserve or restore C/EBPα function could bolster CAMP expression and enhance immune defenses against HMPV. Furthermore, understanding how pathogens exploit transcription factors like C/EBPα may lead to broader insights into immune regulation and pathogen-host interactions.
Conclusions
This study is a landmark in understanding how human metapneumovirus interacts with the immune system. The findings demonstrate that HMPV suppresses CAMP expression in human macrophages by downregulating the transcription factor C/EBPα. This suppression is independent of the vitamin D pathway and interferon signaling, emphasizing a unique viral strategy for immune evasion.
By revealing the mechanisms underlying CAMP suppression, the study contributes to a deeper understanding of the immune system’s complexity and vulnerabilities. It underscores the need for further research into how pathogens manipulate immune responses and how these insights can inform new therapeutic approaches.
The study findings were published in the peer-reviewed journal: Frontiers in Immunology.
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00902/full
For the latest HMPV News, keep on logging to Thailand Medical News.
Read Also:
https://www.thailandmedical.news/news/insights-into-how-human-metapneumovirus-hmpv-spreads-between-cells
https://www.thailandmedical.news/news/human-metapneumovirus-mimic-human-rna-to-evade-immune-defenses
https://www.thailandmedical.news/news/persistence-of-human-metapneumovirus-and-its-role-in-th2-immune-skewing
https://www.thailandmedical.news/news/human-metapneumovirus-hmpv-and-sugar-structures-on-human-cells
https://www.thailandmedical.news/articles/hmpv-human-metapneumovirus
Share
Tweet
Share
