Researchers at the University of Bonn have developed an innovative method to observe how immune receptors, specifically Toll-like receptors (TLRs), detect infections. This advancement could accelerate the search for new treatments for infectious diseases, cancer, diabetes, and dementia. The findings were published in the journal Nature Communications.
TLRs are abundant on the surface of various cells, particularly those in mucous membranes and the immune system. These receptors act like sniffer dogs, identifying infections by responding to specific chemical signals. Upon activation, TLRs initiate a cascade of cellular reactions. For example, when immune scavenger cells detect bacteria, they engage in phagocytosis, engulfing and digesting the pathogens, while other immune cells release signaling molecules that recruit additional immune defenses and trigger inflammation.
Different groups of TLRs respond to various “danger signals,” which have evolved over time. Professor Günther Weindl from the Pharmaceutical Institute at the University of Bonn explains, “These are molecules that have crystallized into important danger signals over the course of evolution,” citing lipopolysaccharides (LPS) from bacterial cell walls as key examples.
Despite this understanding, the precise responses elicited by different signals remain unclear. “It’s quite possible that different molecules stimulate the same TLR but trigger different responses,” Weindl notes. Traditionally, researchers have used color-coded markers to track signaling pathways activated by TLRs, a method that is both time-consuming and requires extensive knowledge of existing pathways.
In contrast, the Bonn researchers employed a novel technique that eliminates the need for color-coding, previously successful in studying other receptors. This method capitalizes on the morphological changes cells undergo upon encountering signal molecules, which prepare them to engulf bacteria or transform into infected tissue.
By placing cells on a specially coated transparent plate and illuminating them with a broadband light source from below, researchers can observe changes in the reflected light spectrum. “We were able to demonstrate that these changes in the reflected wavelengths occur just minutes after adding the signal molecule,” said Dr. Janine Holze, a colleague of Weindl. The study involved exposing cells to lipopolysaccharides from E. coli and Salmonella. Although both types of LPS stimulate the same TLR, the reflected light spectrum varied significantly between the two, indicating that different molecules activate the receptor in distinct ways, leading to specific cellular responses.
Conclusion
This new method offers a more nuanced understanding of TLR function and simplifies the search for potential drugs with targeted actions. “Possible applications include enhancing the immune response to enable the body to more effectively combat cancer cells,” Weindl explained. Conversely, for conditions such as diabetes, rheumatism, or Alzheimer’s disease, the goal may be to dampen certain immune responses that could harm healthy tissues. This innovative approach could bring researchers closer to achieving these therapeutic objectives.
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