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Scientists Discover How an Infectious Parasite Manipulates Immune Cells to Survive – Leading to Skin Ulcers to Enlarged Liver and Even Death

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Breakthrough Discovery: Uncovering How Leishmania Parasites Elude Detection, Leading to Leishmaniasis

Researchers from the University of Calgary have made a significant breakthrough in understanding how Leishmania parasites effectively stay hidden within the human body, causing the debilitating disease known as Leishmaniasis.

These minute parasites are transmitted by infected sandflies and afflict 1 to 2 million individuals in over 90 countries each year. The effects of the disease range from skin ulcers to the enlargement of vital organs such as the spleen and liver, and in severe cases, even death.

Early detection of this chronic disease has proven challenging due to a limited understanding of the parasite’s manipulative mechanisms on immune cells. However, a recent study published in The Journal of Immunology sheds light on this elusive process.

Dr. Nathan Peters, Ph.D., associate professor at the Cumming School of Medicine (CSM) and the principal investigator, highlights the significance of their findings: “This is the first study that shows how the parasite stalls the process of regular neutrophil cell death which prevents the immune system from being activated,”

White blood cells known as neutrophils are the body’s first line of defense against illness and infection. Researchers in the laboratory of Dr. Peters discovered that the parasite targets a receptor on the surface of the neutrophil to enter the cell.

Once inside, the parasite successfully evades the neutrophil’s pathogen-killing molecules, establishing a niche within the immune cell. The remarkable part is that the parasite tricks the neutrophil into mimicking a dying cell, a process that occurs naturally and does not trigger an immune response.

The neutrophil “then acts like a little Trojan Horse,” according to Peters.

The parasite finds a niche inside these neutrophils and makes the neutrophil look like it is a regular dying cell, a process that happens constantly and therefore doesn’t activate the immune system. By stalling the cell death process within the neutrophil, the parasite manages to persist and establish infection.

Previous attempts to develop effective vaccines against Leishmaniasis have been hindered by the parasite’s manipulative tactics.

“The parasite’s behavior interferes with our ability to vaccinate, because the immune system isn’t even aware that the parasite is there,” adds Dr. Peters.

This groundbreaking research was conducted using a specialized laboratory known as the Insectary, located within Peters’ lab. It allowed researchers to raise sand flies infected with the Leishmania parasite, facilitating the study’s progress.

Adam Ranson, the first author, emphasizes the significance of their findings in terms of vaccine development: “Understanding the earliest interactions between the parasite and the host helps explain why previous vaccination strategies against Leishmaniasis have been unsuccessful. Our findings will contribute to bringing researchers closer to developing an effective vaccine against Leishmania infection.”

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