Ep. 99: “Inflammation and Innate Immunity” Featuring Dr. Luke O’Neill
Feb 25, 2025
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Dr. Luke O’Neill, a biochemistry professor at Trinity College Dublin, dives deep into the world of inflammation and innate immunity. He explores how macrophages influence inflammatory responses and their potential role in treating nerve damage. The conversation includes exciting findings about T-cells in asthma and novel anti-inflammatory therapies being developed. O'Neill also discusses the burgeoning field of immunometabolism, where metabolism intersects with immune functionality, shedding light on future treatments for various diseases.
The podcast highlights the essential role of toll-like receptors in initiating immune responses and bridging innate and adaptive immunity.
Research reveals that Granzyme K, produced by CD8 T cells, exacerbates airway inflammatory diseases, suggesting interventions could improve lung function.
Effective communication of scientific knowledge to the public is essential for fostering understanding and support for science, especially post-health crises.
Deep dives
Innate Immunity and Toll-like Receptors
The discussion focuses on the role of toll-like receptors (TLRs) in innate immunity, particularly their function in recognizing pathogens and activating immune responses. TLRs are essential for identifying diverse microbial patterns and initiating inflammation, bridging the innate and adaptive immune systems. This includes the processes of signal transduction that dictate how cells respond to immune challenges. Future research is anticipated to uncover more complex interactions between TLRs and various immune mediators.
Granzyme K's Role in Airway Inflammation
Research indicates that Granzyme K, primarily produced by CD8 T cells, contributes to recurrent airway inflammatory diseases such as asthma and chronic rhinosinusitis. This serine protease facilitates inflammation through its ability to cleave complement proteins, thus promoting immune cell recruitment to the airways. In studies involving patients with nasal polyps, an increased presence of Granzyme K-expressing T cells was linked to more severe symptoms and complications. Interventions targeting Granzyme K have shown potential in reducing inflammatory responses and improving lung function.
Macrophage Plasticity and Graft-versus-Host Disease
The findings emphasize the critical role of macrophages in managing graft-versus-host disease (GVHD), a common complication following bone marrow transplants. Macrophages exhibit heterogeneous properties during GVHD, exhibiting both pro-inflammatory and regulatory functions depending on the context. The research specifically highlights how IL-34 derived from intestinal epithelial cells reprograms macrophages to adopt a protective phenotype, thereby mitigating intestinal inflammation. In models lacking IL-34, inflammation was significantly worse, reinforcing the importance of macrophage signaling in graft acceptance.
Metabolic Reprogramming of Immune Cells
Metabolic reprogramming in immune cells is emerging as a pivotal aspect of their function and response. The research underscores how immune cells, particularly macrophages, shift their metabolism from oxidative phosphorylation to glycolysis during activation to rapidly generate ATP and support inflammatory responses. This metabolic shift is crucial for effective immune functioning but can also lead to pathological conditions if uncontrolled. The collaboration between signaling pathways and metabolic alterations offers a deeper understanding of immune cell behavior during various physiological and pathological states.
Communication and Science Outreach
Effective communication of scientific knowledge to the public is emphasized as an essential function of scientists, especially in light of recent global health crises. The podcast discusses the importance of engaging with audiences outside of the academic realm to foster understanding and support for science. This includes sharing findings from research, addressing public misconceptions, and promoting scientific literacy. Engaging with the community helps build trust and highlights the relevance of scientific work in everyday life, particularly regarding health and environmental issues.
Dr. Luke O’Neill is a Professor and Chair of Biochemistry at Trinity College Dublin, where his research group is focused on exploring the molecular basis of inflammation. His lab endeavors to provide a better understanding of the metabolic regulation of immune cell function and the innate immune system, with the aim of developing novel therapies to treat inflammatory diseases.
A Phage Counter-Defense – An orphan antitoxin counter-defense element has been discovered in phages that can overcome a bacterial toxin-antitoxin phage defense system. (5:40)
Pathogenic Memory T Cells – Researchers uncover a pathogenic subset of CD8+ memory T-cells that promote tissue inflammation. (14:05)
A New Treatment Path for Nerve Damage – Research suggests that macrophages may play a protective role in preventing neuropathy from developing. (30:19)
, taking place May 3-7 in Honolulu, Hawaii.
