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Oxford researchers have unveiled new insights into the ongoing evolutionary battle between humans and the malaria parasite. The international team has discovered how the malaria parasite evades the immune system—and how the human body fights back.

Mosquito on skin © SHUTTERSTOCK

‘Natural killer’ (NK) cells, a key component of the immune system, patrol the body to identify and destroy infected or abnormal cells. These cells rely on a balance of activating and inhibitory receptors to determine whether a cell is friend or foe. When these natural killer cells encounter a pathogen, activating receptors trigger a lethal response, while inhibitory receptors prevent attacks on the body’s own cells.

The malaria parasite Plasmodium falciparum, responsible for the deadliest form of the disease, has evolved a cunning strategy to escape detection. It disguises infected red blood cells with a diverse family of proteins known as RIFINs, originally discovered at Oxford University. Some RIFINs bind to inhibitory receptors like LILRB1 on natural killer cells, effectively disarming them.

The latest study, published in Nature, is a collaboration between scientists from the Kennedy Institute, Osaka University, and the Department of Biochemistry at Oxford. Akihito Sakoguchi, Shiroh Iwanaga, and Hisashi Arase from Osaka—identified a new subset of RIFINs that bind to another inhibitory receptor, or “killer immunoglobulin-like receptors”, called

KIR2DL1. Structural studies led by Sam Chamberlain at the Biochemistry Department then revealed how these RIFINs interact with KIRs, and further studies with Alex Mørch, Marcus Widdess and Prof Michael Dustin from the Kennedy Institute demonstrated that this interaction suppresses natural killer cell activity.

 

 

Read the full story on the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences website.