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| 10.05.2021

A matter of communication: Breloer research group clarifies immune reaction to worm parasites

Worm infections are among the most common tropical diseases worldwide. Parasitic worms are such successful infectious agents partly because they are able to weaken the immune response of their host. But the host also knows what to do: It reacts with a complex interplay of different messenger substances of the immune system.

The important mast cell in red in the intestinal villus

According to estimates by the World Health Organisation (WHO), about a quarter of the world's population is infected with parasitic worms, so-called helminths. These infections are often chronic and have a significant impact on the quality of life and productivity of infected people. Even though most worm infections can be treated with medication, new infections regularly occur in the respective countries and occasionally resistance develops. An effective protective vaccination does not yet exist.

The research group led by Breloer at the Bernhard-Nocht-Institute for Tropical Medicine (BNITM) has now discovered that the alarm signal molecule interleukin-33 (IL-33) plays a special role in this process (Meiners, Reitz, Rüdiger et al., PLOS Pathogens 2020). When they blocked IL-33 with an inhibitor, the researchers observed a significantly lower activity of the body's own immune defence, more precisely the so-called mast cells in the intestine. As a result, the number of parasites increased. If, on the other hand, they stabilised IL-33 or increased its concentration, this increased mast cell activation and the number of parasites in the intestine decreased.


Course of events: The worm releases the alert molecule IL-33 in the tissue. This activates ILC2. This in turn, via another messenger interleukin 9, activates the mast cells that mediate the rejection from the intestine. Interestingly, this rapid defence runs independently of the otherwise so important B and T cells of the adaptive immune system. The group was also able to rule out the involvement of eosinophils, basophils and neutrophil granulocytes.

 

"How exactly does the specific immune response that leads to parasite rejection work? This is the question that drives us. Because if we understand this even better, more effective drugs can be launched to better treat chronic helminth infections, for example," says Breloer, head of the research group at BNITM. The mouse model helps to investigate the complex sequence of events during an infection in more detail and to make a contribution to global health with the help of the knowledge gained, she adds.


Original publication

Meiners, Reitz, Rüdiger et al., “IL-33 facilitates rapid expulsion of the parasitic nematode Strongyloides ratti from the intestine via ILC2- and IL-9-driven mast cell activation”.  PLOS Pathogens (Dez. 22, 2020). https://doi.org/10.1371/journal.ppat.1009121


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