NET amyloidogenic backbone in human activated neutrophils
L Pulze1, B Bassani1,2, E Gini1
1Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.
Clinical and Experimental Immunology
|October 15, 2015
Summary
Neutrophil extracellular traps (NETs) form a resistant, amyloid-like scaffold to trap pathogens. This innate immune response, regulated by reactive oxygen species (ROS), is conserved across species and offers therapeutic potential.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Activated human neutrophils generate neutrophil extracellular traps (NETs), a DNA-based network for pathogen defense.
- NETs possess a resistant, amyloidogenic backbone that sequesters proteins and DNA against non-self entities.
- Amyloid fibril formation in neutrophils is modulated by cytoplasmic reactive oxygen species (ROS) imbalance.
Purpose of the Study:
- To investigate the structural and functional characteristics of NETs as an innate immune mechanism.
- To explore the role of reactive oxygen species (ROS) in regulating NET formation and associated cellular responses.
- To compare neutrophil responses in humans and invertebrates, highlighting conserved defense strategies.
Main Methods:
- Morphofunctional and quantitative evaluation of activated human neutrophils.
- Analysis of reactive oxygen species (ROS) signaling pathways.
- Comparative study of immune cell responses in human and invertebrate models.
Main Results:
- Neutrophil extracellular traps (NETs) exhibit a resistant amyloidogenic backbone.
- Reactive oxygen species (ROS) imbalance regulates amyloidogenesis and stress-associated responses like autophagy and cytokine synthesis.
- Similar amyloidogenic scaffold formation is observed in activated invertebrate immune cells for pathogen defense.
Conclusions:
- NETs represent a primitive yet potent innate defense mechanism in humans, involving amyloid fibril formation.
- The conserved amyloidogenic scaffold mechanism in both human and invertebrate immune cells underscores its evolutionary significance.
- Understanding NET structure and regulation may lead to novel diagnostic and therapeutic strategies for immunomediated diseases.
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