Pruritus, or persistent itch, is an essential sensory alarm that can signal the presence of skin infections, according to neuroimmunologist Juan Inclan-Rico of the University of Pennsylvania. In a recent study published in Nature Immunology, De’Broski Herbert and his team demonstrated how the parasitic worm Schistosoma mansoni can evade the body’s itch response, allowing it to enter the body undetected. The researchers discovered that activating neurons associated with immunity and itchiness can block the entry and dissemination of parasites, providing new insights into sensory immunity and potential strategies for treating parasitic infections.
By investigating the neuronal activity in mice exposed to S. mansoni, the researchers found that activating MrgprA3 neurons blocked the entry of parasites into the body. They also observed that the release of the neuropeptide CGRP played a crucial role in neuron-immune cell communication, triggering an inflammatory response that helps contain the parasite. Additionally, they discovered that the nuclear protein IL-33 within macrophages controls the accessibility of DNA, allowing for the expression of pro-inflammatory cytokines that form a protective barrier against parasite invasion.
The study also revealed that different strains of mice exhibited varying susceptibility to S. mansoni infection, leading the researchers to investigate how avian schistosomes triggered a strong itch response while S. mansoni did not. By using an anti-malarial drug known to cause itchiness and reducing the population of MrgprA3 neurons in mice exposed to S. mansoni antigens, the team demonstrated that itching could be blocked almost entirely. This finding suggests that parasites have evolved mechanisms to suppress the itch response and enter the body undetected, highlighting the need for new therapeutic approaches.
The researchers plan to further explore the molecules that parasites use to suppress neurons and evade the itch response, with the hope of developing more effective treatments for parasitic infections. They also aim to identify other molecules involved in the signaling pathway between neurons and immune cells to potentially provide relief for other itch-related conditions like eczema or psoriasis. By understanding the mechanisms behind neuron-immune communication, the Herbert lab seeks to uncover new insights into sensory immunity and develop innovative therapeutic strategies for combating parasitic infections and other skin conditions.
The research team, consisting of members from the University of Pennsylvania, Charles University, Columbia University, and the Monell Chemical Senses Center, was supported by grants from the National Institutes of Health, Charles University, and the Czech Science Foundation. Their findings shed light on the complex interplay between sensory immunity and parasite invasion, opening up new possibilities for treating parasitic infections and other conditions characterized by persistent itchiness. Through further research and exploration of signaling pathways, the researchers hope to uncover novel therapeutic targets that can improve the treatment of parasitic infections and enhance understanding of the body’s immune response to pathogens.