Phagocytosis-independent antimicrobial activity of mast cells by formation of extracellular traps: cellular receptors involved and underlying molecular mechanism

Summary

It has been increasingly recognized that mast cells are critical components of host defense against pathogens. We have recently described a completely novel mechanism used by mast cells to kill bacteria such as Streptococcus pyogenes or Staphylococcus aureus. This mechanism consists on entrapping them in extracellular structures similar to the extracellular traps described for neutrophils. The mast cells extracellular traps (MCETs) are composed of DNA, histones, tryptase, and the anti-microbial peptide LL-37. Formation of MCETs is not the result of passive release of DNA and granule proteins during cellular disintegration but rather an active and controlled process in response to specific stimulation and strongly dependent on the production of reactive oxygen radicals (ROS). This type of death has been recently termed "Etosis". Etosis is neither typical apoptosis nor necrosis and it is characterized by disintegration of the nuclear membrane concomitant with cytoplasmic granule dissolution, allowing the components of the traps to mix in the cytoplasm before been released.

The goals of this grant proposal are the characterization of the mast cell receptors and bacterial factors triggering the formation of MCETs as well as the characterization of the downstream molecular mechanisms, specifically how ROS trigger mast cell death.

This knowledge will further our understanding about the anti-microbial activity of mast cells and their contribution to host defense against infectious pathogens.

Figure 1. Field emission scanning electron microscopy photograph showing uninfected (left) and S. pyogenes-infected mast cells (right). Notice the formation of MCETs by infected mast cells (arrow).

Figure 2. Left, immunostaining of MCETs with Alexa-red-labelled antibodies against histones. S. pyogenes is labelled green and mast cells nuclei appears in blue. Right, field emission scanning electron microscopy photograph showing S. pyogenes (arrows) entrapped in MCETs.

Figure 3. Induction of MCETs by Staphylococcus aureus (left) or Pseudomonas aeruginosa (right).

Project Team and contact information

PD Dr. Eva Medina
Head of Infection Immunology Research Group
Helmholtz Center for Infection Research
Inhoffenstra├če 7
38124 Braunschweig
Germany

phone: +49 531 6181 4500
fax: +49 531 6181 4499

mail: eva.medina(at)helmholtz-hzi.de
www.helmholtz-hzi.de

Dr. Oliver Goldmann
Infection Immunology Research Group
Helmholtz Center for Infection Research
Inhoffenstra├če 7
38124 Braunschweig
Germany

phone: +49 531 6181 4503
fax: +49 531 6181 4499

mail: oliver.goldmann(at)helmholtz-hzi.de
www.helmholtz-hzi.de

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