Vibrio cholerae Evades Neutrophil Extracellular Traps by the Activity of Two Extracellular Nucleases

PLoS Pathogens

Stefan Schild¹  Ava Hosseinzadeh²  Andreas Grutsch³  Andrea Seper³  Deborah R. Leitner³  Marc Röhm³  Sandro Roier⁴  Joachim Reidl⁵  Gregor Gorkiewicz⁵  Sabine Lichtenegger⁶  Constantin F. Urban⁶ 

[1] Department of Clinical Microbiology, Umeå University, Umeå, Sweden;Department of Molecular Biology, Umeå University, Umeå, Sweden;Institute of Molecular Biosciences, University of Graz, Graz, Austria;Institute of Pathology, Medical University of Graz, Graz, Austria;Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden;Umeå Centre for Microbial Research, Umeå University, Umeå, Sweden

关键词: Neutrophils;    Vibrio cholerae;    Nucleases;    Mouse models;    Cholera;    Inflammation;    Gastrointestinal tract;    Deoxyribonucleases;   

DOI  :  10.1371/journal.ppat.1003614

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY