Classical ROS-dependent and early/rapid ROS-independent release of Neutrophil Extracellular Traps triggered by Leishmania parasites

Natalia C. Rochael, Anderson B. Guimarães-Costa, Michelle T. C. Nascimento1, Thiago S. DeSouza-Vieira1, Matheus P. Oliveira, Luiz F. Garcia e Souza, Marcus F. Oliveira & Elvira M. Saraiva1

Scientific reports. Dec 17, 2014

Speaker: Po-Liang, Chu (朱珀亮)                                        Time: 13:00~14:00, Apr 27 2016

Commentator: Dr. Chi-Chang, Shieh (謝奇璋 醫師)  Place: Room 601

Abstract:

Leishmania is a genus of trypanosomes that are responsible for the disease leishmaniasis. They are spread by sandflies of the genus Lutzomyia in the world. Netosis is one of these mechanisms and occurs with the release of a scaffold of chromatin associated with different granular and intracellular proteins, named neutrophil extracellular traps (NETs) which ensnare and kill microorganisms. Here, the authors analyze the role of neutrophil elastase (NE), myeloperoxidase (MPO), reactive oxygen species (ROS) and Peptidyl arginine deiminase 4 (PAD4) in the netosis stimulated by Leishmania amazonensis promastigotes in human neutrophils. The molecular mechanisms behind NET formation are still poorly understood.There are two main NET release mechanisms have been proposed: the classical, reactive oxygen species (ROS)-dependent and the early/rapid ROS-independent. Their results demonstrate that Leishmania promastigotes trigger the classical netosis, by promoting redox imbalance, with the involvement of NADPH-oxidase and NOS derived ROS/RNS, respectively. This mechanism is also dependent on PAD4 and elastase activity. Furthermore, promastigotes promoted the early/rapid, ROS-independent NET formation occurring only 10 minutes after neutrophil-parasite interaction, which is dependent of elastase, but not on PAD4. Further studies are required to better understand how neutrophil redox mechanisms triggered by Leishmania induced NET formation, the dynamics of this process and their consequences for the host immune system and potential as therapeutic target for leishmaniasis.

Reference:

1. Brinkmann, V. U. et al. Neutrophil extracellular traps kill bacteria. Science 303, 1532–1535 (2004).

2. Fuchs, T. A. et al. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol 176, 231–241 (2007).