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Updated: Feb 11, 2026

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
[PMNDTR mice: a new model to study neutrophils in vivo]
Caitlin M Gillis1, Laurent L Reber1
1Institut Pasteur, Département d'immunologie, Inserm U1222, Unité des anticorps en thérapie et pathologie, 25, rue du Docteur Roux, 75015 Paris, France.
Abstract:
Neutrophils play a key role in host defense against pathogens. They can contribute to pathological inflammation, and are thought to exacerbate tissue injury upon exposure to bacterial products, such as endotoxin (LPS). Recent findings suggest that neutrophils can also participate in adaptive immune responses and contribute to inflammation resolution. Many discoveries regarding the in vivo role of neutrophils were made possible by the use of genetically modified neutrophil-deficient mice, or by the use of neutrophil-depleting antibodies. Here we describe a new mouse model, PMNDTR mice, in which neutrophils can be selectively depleted upon injection of diphtheria toxin. Using this model, we have recently demonstrated that neutrophils play a protective role during lethal endotoxin-induced systemic shock. This new mouse model presents several major advantages over more classical models of neutropenia, which are discussed herein.
Insights
Neutrophils protect against lethal endotoxin shock. A new mouse model allows selective neutrophil depletion, revealing their crucial protective role in systemic inflammation and offering advantages over older methods.
Area of Science:
- Immunology
- Host Defense Mechanisms
- Inflammation Biology
Background:
- Neutrophils are critical for pathogen defense but can also cause tissue injury during inflammation.
- Existing methods for studying neutrophils in vivo, like genetic modification or antibody depletion, have limitations.
- The role of neutrophils in adaptive immunity and inflammation resolution is an emerging area of research.
Purpose of the Study:
- To introduce and validate a novel mouse model (PMNDTR) for selective neutrophil depletion.
- To investigate the in vivo role of neutrophils in endotoxin-induced systemic shock using the new model.
- To highlight the advantages of the PMNDTR model compared to traditional neutropenia models.
Main Methods:
- Development of the PMNDTR mouse model, enabling neutrophil depletion via diphtheria toxin injection.
- Utilizing the PMNDTR model to study the effects of neutrophil depletion on endotoxin-induced systemic shock.
- Comparative analysis of the PMNDTR model against established neutropenia models.
Main Results:
- Demonstrated that neutrophils play a significant protective role during lethal endotoxin-induced systemic shock.
- The PMNDTR mouse model allows for precise and selective depletion of neutrophils.
- The new model offers substantial advantages over classical methods for studying neutrophil function in vivo.
Conclusions:
- Neutrophils are essential for host survival during severe inflammatory responses like endotoxin shock.
- The PMNDTR mouse model is a valuable tool for dissecting neutrophil functions in various physiological and pathological contexts.
- This model facilitates a deeper understanding of neutrophil contributions to both host defense and inflammatory diseases.
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