New research from the University of Pittsburgh has uncovered a novel mechanism by which the immune system combats intestinal parasitic worms, or helminths. This discovery, published today in the journal Immunity, suggests that common non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, could be repurposed to enhance immunity against these widespread infections.
Helminths are among the most prevalent infections globally, particularly in regions with limited access to clean water and sanitation. “While parasitic worms are less of an issue in most of the U.S. and other wealthy nations, these infections affect almost a quarter of the world’s population,” said Dr. Reinhard Hinterleitner, co-senior author and assistant professor in the Pitt Department of Immunology. “There hasn’t been a new medication developed to treat parasites for decades, so there is a huge need for novel treatments.”
Understanding the Immune Response
The study delves into the different types of immune responses, as explained by Dr. Yi-Nan Gong, co-senior author and assistant professor in the Pitt Department of Immunology. Type 1 immunity is known for its role in directly attacking viruses and bacteria. In contrast, type 2 immunity offers a broader defense against external threats such as parasites. However, this response can also be erroneously activated, leading to food and environmental allergies.
“Type 2 immunity is like an eviction campaign,” Gong elaborated. “By driving inflammation and accelerating cell turnover and differentiation, it makes the gut environment inhospitable for parasites, naturally expelling them.”
The Role of Gasdermin C
To further investigate type 2 immunity in response to helminths, the researchers focused on a protein called Gasdermin C. Typically found at low levels in the healthy gut, Gasdermin C increases in response to parasitic infection. Gasdermins remain inactive until cleaved by an enzyme known as a protease, releasing an active protein fragment.
The team discovered that a protease called Cathepsin S activates Gasdermin C in both mice and humans. Disabling either Gasdermin C or the protease impaired type 2 responses to helminth infections in mice, underscoring their essential role in immunity to parasites.
Implications for Treatment
Once activated, most gasdermins trigger cell death, eliminating infected cells and recruiting immune cells. However, Gasdermin C behaves differently. The active fragment of Gasdermin C targets Rab7-positive vesicles, reducing levels of a chemical messenger called prostaglandin d2, which dampens type 2 responses. By lowering prostaglandin d2, Gasdermin C enhances immunity and clears parasitic infections.
“This finding offers new perspectives for anti-parasitic therapies,” Gong explained. “One promising approach involves cyclooxygenase (COX) inhibitors. Prostaglandin d2 synthesis depends on COX. Common COX inhibitors, including NSAIDs like ibuprofen, are widely used and safe for both adults and children.”
Despite these promising findings, the researchers emphasized the need for clinical trials to confirm the effectiveness of this approach in humans. They cautioned that individuals should consult healthcare providers before starting any new medications.
Broader Implications and Future Research
The study also highlighted the role of commensal gut microbes—typically harmless residents of the intestine—in triggering type 2 immunity in mice. This suggests that under certain conditions, such as food allergies and inflammatory bowel disease (IBD), these microbes may contribute to symptoms driven by type 2 immune responses.
“The gut microbiome plays an important role in the development of food allergies and IBD,” noted Hinterleitner. “It is possible that, with further study, identifying microbes that induce Gasdermin C could be used as a marker or predictor of the risk of food allergies.”
The research was supported by various institutions, including the Department of Immunology Investigator Start-up Fund, the National Institutes of Health, and international foundations. As the scientific community continues to explore these findings, the potential for new therapeutic strategies against parasitic infections and related immune conditions remains a promising frontier.
