Related Experiment Video
Updated: May 24, 2025
Fast and Specific Assessment of the Halogenating Peroxidase Activity in Leukocyte-enriched Blood Samples
Published on: July 28, 2016
Major basic protein and eosinophil peroxidase support microfilariae motility inhibition by eosinophil ETosis
Pia Philippa Schumacher1, Jesuthas Ajendra1, Benjamin Lenz1
1Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.
Abstract:
Eosinophils are a hallmark of filarial infections. They are primary effector cells and can attack filariae by releasing extracellular traps that contain toxic cationic proteins, such as eosinophil peroxidase and major basic protein. Previous studies demonstrated that the extracellular traps of eosinophils are induced by the microfilariae of Litomosoides sigmodontis and that they inhibit their motility. In this project, we aimed to investigate the role of these cationic proteins during the extracellular trap-mediated immobilization of microfilariae. Our results indicate that extracellular DNA traps from knockout mice that lack eosinophil peroxidase or major basic protein are significantly less able to immobilize and kill microfilariae. Accordingly, the addition of these cationic proteins to in vitro cultures inhibited microfilariae motility in a dose-dependent manner. Moreover, we examined eosinophils from the natural host, the cotton rat Sigmodon hispidus. While eosinophils of cotton rats release DNA after stimulation with PMA and zymosan, microfilariae did not trigger this effector function. Our work shows that eosinophil granule proteins impair the motility of microfilariae and indicate significant differences in the effector functions of eosinophils between the mouse model and the natural host. We hypothesize that the absence of DNA nets released by cotton rat eosinophils in response to microfilariae may explain the higher microfilarial load and longer patency of the natural host.
Insights
Eosinophil cationic proteins, like eosinophil peroxidase and major basic protein, are crucial for immobilizing and killing filarial parasites. Differences in eosinophil function between mouse models and natural hosts may explain parasite load.
Area of Science:
- Immunology
- Parasitology
- Cell Biology
Background:
- Eosinophils are key effector cells in filarial infections, attacking parasites via extracellular traps.
- These traps contain toxic cationic proteins, including eosinophil peroxidase (EPX) and major basic protein (MBP).
- Previous studies show eosinophil extracellular traps (EETs) induced by microfilariae inhibit parasite motility.
Purpose of the Study:
- To investigate the specific role of cationic proteins in EET-mediated immobilization of microfilariae.
- To compare eosinophil effector functions between a mouse model and the natural host, the cotton rat.
Main Methods:
- Utilized knockout mice lacking EPX or MBP to assess the impact on EET-mediated microfilarial immobilization and killing.
- Conducted in vitro experiments adding purified cationic proteins to microfilariae cultures.
- Examined eosinophil responses from cotton rats (Sigmodon hispidus) upon stimulation with PMA, zymosan, and microfilariae.
Main Results:
- EETs from EPX- or MBP-deficient mice showed significantly reduced ability to immobilize and kill microfilariae.
- Cationic proteins inhibited microfilarial motility in a dose-dependent manner in vitro.
- Cotton rat eosinophils released DNA upon stimulation with PMA and zymosan but not microfilariae.
Conclusions:
- Eosinophil granule proteins are essential for impairing microfilarial motility.
- Significant differences exist in eosinophil effector functions between the mouse model and the natural host.
- The lack of microfilariae-induced DNA nets in cotton rat eosinophils may contribute to higher parasite loads and longer patency.
More Related Videos
Related Concept Videos
01:24Microtubules in Cell Motility
01:39Mechanism of Filopodia Formation
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
01:05Mechanism of Ciliary Motion
The cilia are made up of microtubules in a 9+2 arrangement, with nine microtubule doublet ring bundles, surrounding a pair of central singlet microtubule bundles. The doublet microtubule bundles are...