An unexpected mechanism regulates the immune response during parasitic infections

Researchers at the University of Liège (Belgium) have uncovered a previously unknown mechanism that regulates the immune response against parasites. During a parasitic infection, specific immune cells, known as virtual memory T cells, become activated and express a surface molecule called CD22, which prevents an excessive immune reaction. This discovery could help in better-controlling inflammation and improving immune responses to infections.

The findings are published in the journal Science Immunology.

Nearly a quarter of the world’s population is infected by helminths, parasitic worms that establish themselves in the intestine for extended periods. In response to these invaders, the immune system deploys complex defense strategies. In their recent study, the researchers revealed a previously unsuspected mechanism that regulates the activation of certain immune cells: CD8+ virtual memory T cells (TVM).

A surprising role for CD22 in T Cell regulation

The researchers found that during helminth infections, a key immune molecule, interleukin-4 (IL-4), strongly stimulates TVM cells, causing their proliferation in the spleen and lymph nodes. TVM cells are immune cells capable of reacting rapidly to viral infections.

In a previous study published in 2018, the research team demonstrated that IL-4 stimulation of TVM cells enhances viral infection control during co-infections with helminths and viruses. However, this intense stimulation of TVM cells during parasitic infection does not appear to play a role in controlling the parasite itself, which intrigued the researchers.

“What is surprising is that this activation of TVM cells is accompanied by the expression of a receptor called CD22, which is normally exclusive to B lymphocytes—another type of white blood cells,” explains Professor Benjamin Dewals from ULiège.

“This receptor plays a crucial role in regulating immune responses. Its presence on TVM cells acts as a brake, limiting their excessive activation and thereby preventing excessive inflammation.”

A delicate balance between defense and regulation

This discovery opens up new perspectives on how the body regulates its immune responses. In addition to their role in combating certain infections, TVM cells activated during parasitic infections also help regulate inflammation. In other words, rather than merely responding to IL-4 produced during the infection, they also work to prevent an overreaction of the immune system.

Understanding this mechanism more precisely could pave the way for new strategies to enhance immune defenses against infections or, conversely, to mitigate excessive inflammatory reactions, which are responsible for certain autoimmune diseases. “Further research is needed to determine whether a similar phenomenon exists in humans and how this discovery could be applied in medicine,” adds Professor Dewals.

This study, conducted in collaboration with researchers from Université Libre de Bruxelles, McGill University (Canada), and the University of Erlangen (Germany), highlights the importance of fundamental research in unveiling the mysteries of the immune system and potentially leading to medical advancements.