Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Seper, A; Hosseinzadeh, A; Gorkiewicz, G; Lichtenegger, S; Roier, S; Leitner, DR; Röhm, M; Grutsch, A; Reidl, J; Urban, CF; Schild, S.
Vibrio cholerae evades neutrophil extracellular traps by the activity of two extracellular nucleases.
PLoS Pathog. 2013; 9(9):e1003614-e1003614
Doi: 10.1371/journal.ppat.1003614
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- Co-Autor*innen der Med Uni Graz
- Gorkiewicz Gregor
- Koller Andrea Christine
- Leitner Deborah Raphaela
- Wagner-Lichtenegger Sabine
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- Abstract:
- The Gram negative bacterium Vibrio cholerae is the causative agent of the secretory diarrheal disease cholera, which has traditionally been classified as a noninflammatory disease. However, several recent reports suggest that a V. cholerae infection induces an inflammatory response in the gastrointestinal tract indicated by recruitment of innate immune cells and increase of inflammatory cytokines. In this study, we describe a colonization defect of a double extracellular nuclease V. cholerae mutant in immunocompetent mice, which is not evident in neutropenic mice. Intrigued by this observation, we investigated the impact of neutrophils, as a central part of the innate immune system, on the pathogen V. cholerae in more detail. Our results demonstrate that V. cholerae induces formation of neutrophil extracellular traps (NETs) upon contact with neutrophils, while V. cholerae in return induces the two extracellular nucleases upon presence of NETs. We show that the V. cholerae wild type rapidly degrades the DNA component of the NETs by the combined activity of the two extracellular nucleases Dns and Xds. In contrast, NETs exhibit prolonged stability in presence of the double nuclease mutant. Finally, we demonstrate that Dns and Xds mediate evasion of V. cholerae from NETs and lower the susceptibility for extracellular killing in the presence of NETs. This report provides a first comprehensive characterization of the interplay between neutrophils and V. cholerae along with new evidence that the innate immune response impacts the colonization of V. cholerae in vivo. A limitation of this study is an inability for technical and physiological reasons to visualize intact NETs in the intestinal lumen of infected mice, but we can hypothesize that extracellular nuclease production by V. cholerae may enhance survival fitness of the pathogen through NET degradation.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Bacterial Proteins - genetics
- Bacterial Proteins - immunology
- Bacterial Proteins - secretion
- Cholera - enzymology
- Cholera - genetics
- Cholera - immunology
- Cholera - pathology
- Deoxyribonucleases - genetics
- Deoxyribonucleases - immunology
- Deoxyribonucleases - secretion
- Female -
- Humans -
- Immunity, Innate - genetics
- Male -
- Mice -
- Mice, Knockout -
- Microbial Viability -
- Neutrophils - immunology
- Neutrophils - metabolism
- Neutrophils - pathology
- Vibrio cholerae - enzymology
- Vibrio cholerae - genetics
- Vibrio cholerae - immunology