Immune system mechanism against filarial larvae

January 20, 2021

Eosinophilic granulocytes are capable of excreting DNA traps to capture microfilariae. The images were taken by fluorescence microscopy. Left: DNA traps (stained orange, arrows) of eosinophil granulocytes. Right: A microfilaria (top) is captured by the DNA trap (stained blue, arrows) of eosinophil granulocytes (roundish structures). © Alexandra Ehrens

 

Researchers at the University of Bonn investigate immune system mechanism against filarial larvae

Filariae, slender but sometimes up to 70 centimeters long nematodes, can set up residence in their host quite tenaciously and cause serious infectious diseases in the tropics. The tiny larvae of the worms are usually transmitted from person to person by mosquitoes, which pick up the larvae from the blood or subcutaneous tissue when they bite and deposit them in the vessels or tissues of their next victim.

Researchers led by the University of Bonn have now investigated a mechanism by which the immune system attacks the filariae. Certain immune cells, the eosinophil granulocytes, release DNA that forms a kind of web around the larvae and traps them. The researchers also identified which protein "turns on" the mechanism, known as the Dectin-1 receptor. The study has been published in the journal Cell Reports.

The study received financial support by the Cluster of Excellence ImmunoSensation.

To investigate which mechanisms the immune system uses against such invaders, in their study the researchers took a closer look at certain immune cells, the eosinophil granulocytes. These cells get their name from the red dye eosin, with which they can be stained. "Eosinophil granulocytes are known to offer a protective effect in filarial infections. However, the exact mechanism was not known until now," says study leader Prof. Marc P. Hübner from the Institute of Medical Microbiology, Immunology and Parasitology at the University Hospital Bonn and the German Center for Infection Research (DZIF).

Using cell cultures, they found that eosinophils reacted to nematode larvae - the cells produced DNA, which then spun around the larvae outside the cell like a web. This meant that the larvae could move only with difficulty or not at all and were thus rendered harmless. The mechanism occurred both in released larvae (first larval stage) and in more developed larvae at an already infectious stage (third larval stage). This could reduce the spread of the parasites, because the transmitting insects subsequently encounter fewer microfilariae. In addition, the infective larvae transmitted by the insect are more effectively controlled in the final host.Receptor recognizes larvae and triggers protective mechanism

But what makes cells recognize the threat of larvae and release DNA webs? The researchers concluded that it is a specific protein on the cell surface, the Dectin-1 receptor. When the cells come into contact with the worm larvae, it is set in motion and triggers the mechanism, which consists of a series of successive signals."Our results demonstrate that eosinophil ETosis is a conserved mechanism. This is demonstrated by the fact that both human and animal eosinophil granulocytes are able to release their DNA when they come into contact with filariae of different species," emphasizes lead author Dr. Alexandra Ehrens from the University of Bonn.

Find here the german and english press release.

Publication: Alexandra Ehrens, Benjamin Lenz, Anna-Lena Neumann, Samuela Giarrizzo, Julia Jennifer Reichwald, Stefan Julian Frohberger, Wiebke Stamminger, Benedikt Christian Buerfent, Frédéric Fercoq, Coralie Martin, Daniel Kulke, Achim Hoerauf & Marc Peter Hübner: Microfilariae Trigger Eosinophil Extracellular DNA Traps in a Dectin-1-Dependent Manner. Cell Reports; DOI: 10.1016/j.celrep.2020.108621

Link to study: https://www.cell.com/cell-reports/pdf/S2211-1247(20)31610-7.pdf

Contact:

Prof. Dr. Marc Hübner
Institute for Medical Microbiology, Immunology and Parasitology
University of Bonn, University Hospital Bonn, German Center for Infection Research
Phone: +49 228 287 19177
Email: huebner@uni-bonn.de

Dr. Alexandra Ehrens
Institute for Medical Microbiology, Immunology and Parasitology
University of Bonn, University Hospital Bonn
Phone: +49 228 287 19155
Email: aehrens@uni-bonn.de