Parasitic worms evolved to suppress neurons in skin

New research, published in The Journal of Immunology, discovered that a parasitic worm suppresses neurons in the skin to evade detection. The researchers suggest that the worm likely evolved this mechanism to enhance its own survival, and that the discovery of the molecules responsible for the suppression could aid in the development of new painkillers.

Schistosomiasis is a parasitic infection caused by helminths, a type of worm. Infection occurs during contact with infested water through activities like swimming, washing clothes, and fishing, when larvae penetrate the skin. Surprisingly, the worm often evades detection by the immune system, unlike other bacteria or parasites that typically cause pain, itching, or rashes.

In this new study, researchers from Tulane School of Medicine aimed to find out why the parasitic worm Schistosoma mansoni doesn’t cause pain or itching when it penetrates the skin. Their findings show that S. mansoni causes a reduction in the activity of TRPV1+, a protein that sends signals the brain interprets as heat, pain, or itching. As part of pain-sensing in sensory neurons, TRPV1+ regulates immune responses in many scenarios such as infection, allergy, cancer, autoimmunity, and even hair growth.

The researchers found that S. mansoni produces molecules that suppress TRPV1+ to block signals from being sent to the brain, allowing S. mansoni to infect the skin largely undetected. It is likely S. mansoni evolved the molecules that block TRPV1+ to enhance its survival.

“If we identify and isolate the molecules used by helminths to block TRPV1+ activation, it may present a novel alternative to current opioid-based treatments for reducing pain,” said Dr. De'Broski R. Herbert, Professor of Immunology at Tulane School of Medicine, who led the study. “The molecules that block TRPV1+ could also be developed into therapeutics that reduce disease severity for individuals suffering from painful inflammatory conditions.”

The study also found that TRPV1+ is necessary for initiating host protection against S. mansoni. TRPV1+ activation leads to the rapid mobilization of immune cells, including gd T cells, monocytes, and neutrophils, that induce inflammation. This inflammation plays a crucial role in host resistance to the larval entry into the skin. These findings highlight the importance of neurons that sense pain and itching in successful immune responses

“Identifying the molecules in S. mansoni that block TRPV1+ could inform preventive treatments for schistosomiasis. We envision a topical agent which activates TRPV1+ to prevent infection from contaminated water for individuals at risk of acquiring S. mansoni,” said Dr. Herbert.

In this study, mice were infected with S. mansoi and evaluated for their sensitivity to pain as well as the role of TRPV1+ in preventing infection. Researchers next plan to identify the nature of the secreted or surface-associated helminth molecules that are responsible for blocking TRPV1+ activity and specific gd T cell subsets that are responsible for immune responses. The researchers also seek to further understand the neurons that helminths have evolved to suppress.

The research article is available in The Journal of Immunology or you can read more on AAI News & Views.

Requests for interviews with authors, The Journal of Immunology or the American Association of Immunologists can be made to kpalmer@aai.org.

About The American Association of Immunologists

The American Association of Immunologists (AAI) is one of the world’s largest organizations of immunologists and scientists in related disciplines. Our mission is to improve global health and well-being by advancing immunology and elevating public understanding of the immune system. AAI members are responsible for some of the most significant biomedical discoveries of the past century, including the development of life-saving cancer immunotherapies, antibody therapies, transplant technologies, and vaccines. We support scientists across the field of immunology through knowledge dissemination, community building, advocacy, and public outreach.

About The Journal of Immunology

The Journal of Immunology (The JI) publishes peer-reviewed manuscripts describing novel findings in all areas of experimental immunology, including both basic and clinical studies. The JI is owned by the American Association of Immunologists and published in partnership with Oxford University Press.

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