Of Worms, the Sense of Taste, and World Health

What is a cell biologist with a “green thumb” for growing intestinal organoids doing working at the Monell Chemical Senses Center, the oldest free-standing research institute for study of taste and smell?

Since 2014, Monell Associate Member Peihua Jiang, PhD has been researching taste-like tuft cells of the gut. These cells express various kinds of taste-signaling molecules, much the same as cells in the human tongue. Recently, tuft cells’ role as immune sentinels has gradually been better appreciated by scientists. This population of cells can become infected by a variety of intestinal parasites, many of which spur the proliferation of tuft and other specialized cells in the small intestine, and ultimately, expelling parasites from the body.

Worm infection remains prevalent in developing countries and represents a significant health burden that negatively affects the development and health of infected children. Tuft cells detect parasites, protozoans, and other infectious microbes via the cell surface receptor Sucnr1, among others, to initiate an immune response.

In 2018, Jiang’s research group found that Sucnr1 is specific to intestinal tuft cells, but the molecular cascade of events leading to the clearance of parasites is not yet fully understood. What is known is that Sucnr1 activation triggers the release of the cytokines to ultimately kill the pathogens. One of the cytokines, IL-25, activates the release of another cytokine, IL13, which contributes to gut tissue remodeling, including the increased reproduction of tuft and goblet cells and the atrophy of villus cells.

A few weeks ago Jiang, Monell visiting graduate student Ranhui Xi, and colleagues from West China Hospital of Stomatology, Sichuan University, USDA, and Tokyo University of Agriculture published the next chapter in this unfolding story. The team used immune cytokines IL-13 and the closely related IL-4 to stimulate intestinal epithelial cells in intestinal organoids and observed a significant up-regulation of the gene gasdermin C. This, in turn, caused a specific type of inflammation-related cell death called pyroptosis.

In this study, mice infected with the parasitic worm Nippostrongylus brasiliensis showed that cell death may be a part of the host defense mechanism to facilitate worm clearance. Tuft cells detect and initiate an immune response against parasites. Upregulation of gasdermin may facilitate worm expulsion, which makes their study very significant for global health. Parasitic infection often leads to malnutrition and retarded growth, since this may involve the shrinking of certain gut cells important for absorbing nutrients.

Looking ahead, “the discovery of this gasdermin activity may provide a pharmaceutical target for treating worm infection in the future,” said Jiang.

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The Monell Chemical Senses Center is an independent nonprofit basic research institute based in Philadelphia, Pennsylvania. Founded in 1968, Monell‘s mission is to improve health and well-being by advancing the scientific understanding of taste, smell, and related senses, where our discoveries lead to improving nutritional health, diagnosing, and treating disease, addressing smell and taste loss, and digitizing chemosensory data.