Does NETosis Contribute to the Bacterial Pathoadaptation in Cystic Fibrosis?

Samir Rahman,Mihaela Gadjeva

doi:10.3389/fimmu.2014.00378

Abstract

Significant advances in our understanding of neutrophil biology were made in the past several years. The exciting discovery that neutrophils deploy neutrophil extracellular traps (NETs) to catch pathogens paved the way for a series of additional studies to define the molecular mechanisms of NET generation and the biological significance of NETosis in acute and chronic pathologic conditions. This review highlights the latest knowledge regarding NET structures, deployment, and function, with an emphasis on current understanding of NET proteomes, their conservation, and significance in the context of cystic fibrosis (CF), a condition characterized by excessive extracellular DNA/NET presence. We also discuss how our understanding of NETosis yields novel therapeutic approaches and their applicability to CF.

Highlights

The significance of the role of neutrophils in infection response has been appreciated since the latter part of the nineteenth century
These conserved proteins included βactin, α-actinin-1/4, α-enolase, filamin-A, histone H2A, histone H2B, histone H4, lactoferrin, MPO, myosin-9, moesin, neutrophil defensin 2, neutrophil elastase, neutrophil gelatinase-associated lipocalin, plastin-2, profilin-1, resistin, glucoso-6-phosphate isomerase, and transketolase (Table 1) [6]. Because of this conservation of the repertoire, we propose to term this neutrophil extracellular traps (NETs)-associated assembly the NET “core proteome”
Given the highly adhesive nature of NETs, the structures likely bound slightly different arrays of proteins in the different environments surrounding each stimulus. This view is consistent with the role of NETosis as a component of the innate immune response, which serves as a rapid defense that is not tailored to different pathogens

Summary

Samir Rahman and Mihaela Gadjeva*

Division of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA. Reviewed by: Martin Herrmann, Universitätsklinikum Erlangen, Germany Anna M. Significant advances in our understanding of neutrophil biology were made in the past several years. The exciting discovery that neutrophils deploy neutrophil extracellular traps (NETs) to catch pathogens paved the way for a series of additional studies to define the molecular mechanisms of NET generation and the biological significance of NETosis in acute and chronic pathologic conditions. This review highlights the latest knowledge regarding NET structures, deployment, and function, with an emphasis on current understanding of NET proteomes, their conservation, and significance in the context of cystic fibrosis (CF), a condition characterized by excessive extracellular DNA/NET presence. We discuss how our understanding of NETosis yields novel therapeutic approaches and their applicability to CF

INTRODUCTION

Findings

Nucleus Enzymes Cytoplasm Peroxisome Cytoskeleton Membrane