TLR9 on red blood cells binds DNA, leading to innate immune activation and anemia.
Red blood cells coated with DNA are internalized by macrophages, triggering immune responses.
Targeting TLR9 on red blood cells may modulate inflammation in anemia, infection, and COVID-19.
Deep dives
Presence of TLR9 on Red Blood Cells and Its Role in Immune Activation
This podcast episode discusses the presence of TLR9 (Toll-like receptor 9) on red blood cells and its role in promoting innate immune activation and anemia. The hosts explain that while red blood cells are primarily known for their oxygen-carrying function, recent research has shown that they also have immune functions, including the binding of complements and immobilizing pathogens. The hosts highlight a study that focused on the binding of DNA to TLR9 expressed on red blood cells, which was found to induce innate immune activation. They discuss how this finding adds to our understanding of the immune functions of red blood cells and the potential implications for diseases associated with inflammation and sepsis.
Interactions between TLR9 on Red Blood Cells and Macrophages
The hosts delve into the interactions between TLR9 on red blood cells and macrophages. They explain that macrophages in the spleen, specifically red pulp macrophages, have been shown to ingest red blood cells that are coated with DNA. They discuss how this internalization of DNA-coated red blood cells triggers the TLR9 receptors in macrophages, leading to immune responses. The hosts mention the potential role of CD47 molecules and other factors in facilitating this interaction. They also touch on the release of interferons and interleukin-6 as part of the immune response.
Implications and Future Directions
The hosts explore the implications of the study's findings and discuss future directions for research. They highlight the potential significance of TLR9-mediated immune responses in the context of diseases such as sepsis and inflammation. The hosts emphasize the need for further investigation, including single-cell analysis to better understand the immune responses and signaling pathways involved in TLR9 interactions with red blood cells and macrophages. They suggest potential experiments to elucidate the mechanisms and consequences of these interactions in more detail.
Red blood cells binding DNA and its biological effects
Red blood cells have been shown to bind and respond to DNA, which can be DNA from microorganisms or self-DNA. The binding of DNA to red blood cells causes changes in their structure and downregulates the molecule CD47. This binding is dependent on the presence of Toll-like receptor 9 (TLR9) on the surface of red blood cells. The binding of DNA to red blood cells can have biological consequences, including increased phagocytosis by macrophages and the induction of pro-inflammatory responses. The study also suggests that targeting TLR9 on red blood cells could potentially modulate inflammation.
Association of red blood cell DNA binding with anemia and infection
The study demonstrates that red blood cell DNA binding is associated with anemia and infection, including COVID-19. Anemic patients and individuals with severe COVID-19 infection have higher levels of DNA bound to their red blood cells. The binding of DNA to red blood cells correlates with the severity of the condition, as measured by the Apache III score. The study also highlights the potential role of red blood cells in delivering DNA to macrophages, triggering inflammatory responses. Targeting red blood cell TLR9 could be a potential strategy for modulating inflammation in these conditions.
Immune reviews evidence that toll-like receptor 9 on the surface of red blood cells binds DNA, leading to uptake by macrophages and innate immune activation.
