Penn State immunology researchers discovered that mice infected with the schistosome parasite’s type I interferon, a protein necessary for the body’s defense against viruses, suppressed inflammation significantly. The disclosure might prompt viable treatments for those experiencing schistosomiasis, second only to jungle fever as the most prevalent parasitic infection internationally.
Parisa Kalantari, partner teacher of immunology in Penn State’s School of Horticultural Sciences, and co-creators have as of late distributed these discoveries in Procedures of the Public Foundation of Sciences.
Schistosomes are parasitic worms that live in water and are the cause of more than 250 million infections in humans worldwide. Schistosomiasis can cause anything from an itchy rash, fever, chills, cough, and muscle aches to severe abdominal pain, an enlarged liver and spleen, and in the worst cases, even death.
“The molecular mechanisms underlying such disparities in pathology are not well understood. My group studies immunological responses and immunopathology in a mouse model of schistosomiasis, which has significant similarities to the human state, to understand more about these molecular pathways.”
Parisa Kalantari, assistant professor of immunology in Penn State’s College of Agricultural Sciences,
Most prevalent in Africa, South America, and Asia, schistosomes live in freshwater, where they can contaminate individuals who go into streams or lakes to chill, swim, or wash. Even if a person has recovered from schistosomiasis, they still have a high risk of reinfection when they return to the water.
Although a medication called Praziquantel is compelling in treating a few cases, certain types of schistosomes are impervious to the medication, and there is no immunization for the sickness. In addition, despite the fact that the majority of people infected with schistosomes develop a mild form of the disease, 5–10% of the time, the disease is severe and can cause death.
“Assuming you consider 5–10% of 250 million individuals, that is still a lot,” Kalantari said. “That is the reason it’s essential to foster more treatments to treat this infection.”
The goal of Kalantari and her graduate students is to learn why some people get the severe form of the disease while others get the mild form.
She stated, “The molecular mechanisms that result in such wide differences in pathology are not well understood.” My lab focuses on studying immune responses and immunopathology in a mouse model of schistosomiasis, which is remarkably similar to the human condition, to learn more about these molecular mechanisms.
According to Kalantari’s explanation, the body’s reaction to the worms’ eggs is the source of many of the symptoms of schistosomiasis. While the majority of the eggs are excreted from the body, some get stuck in various body tissues and cause damage to organs like the liver. Invulnerable cells get a move on in an attempt to dispose of the schistosome eggs. Granulomas, also known as areas of inflammation or tightly clustered immune cells, are the result of this immune response.
An immune mechanism that prevents the host from developing severe immunopathology was discovered by Kalantari and her colleagues. This mechanism results in smaller granulomas and less inflammation.
According to Kalantari, “So we can see that type I interferon is important for decreasing and suppressing inflammation” and that it protects the host.
During their examination, Kalantari and her partners found a second component that influences a safe reaction to schistosomes in the host. They tracked down elevated levels of gasdermin D, a protein included when the safe framework answers contamination more forcefully than it ought to, in unambiguous resistant cells from mice with extreme illness. Inflammation and severe disease can result from this inflammatory molecule suppressing the protective type I interferon pathway.
Kalantari’s discoveries address a huge development in grasping these two sub-atomic pathways.
She stated, “Understanding how these pathways function could lead to the identification of strategies, such as interferon therapy, that could treat schistosomiasis and other inflammatory conditions, with implications for human health.”
More information: Parisa Kalantari et al, The balance between gasdermin D and STING signaling shapes the severity of schistosome immunopathology, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2211047120
