| Full text | |
| Author(s): Show less - |
Toller-Kawahisa, Juliana Escher
;
Hiroki, Carlos Hiroji
;
Silva, Camila Meirelles de Souza
;
Nascimento, Daniele Carvalho
;
Publio, Gabriel Azevedo
;
Martins, Timna Varela
;
Damasceno, Luis Eduardo Alves
;
Veras, Flavio Protasio
;
Viacava, Paula Ramos
;
Sukesada, Fabio Yuji
;
Day, Emily Anne
;
Zotta, Alessia
;
Ryan, Tristram Alexander Jasper
;
da Silva, Rodrigo Moreira
;
Cunha, Thiago Mattar
;
Lopes, Norberto Peporine
;
Cunha, Fernando de Queiroz
;
O'Neill, Luke Anthony John
;
Alves-Filho, Jose Carlos
Total Authors: 19
|
| Document type: | Journal article |
| Source: | NATURE COMMUNICATIONS; v. 14, n. 1, p. 16-pg., 2023-07-17. |
| Abstract | |
Neutrophils rely predominantly on glycolytic metabolism for their biological functions, including reactive oxygen species (ROS) production. Although pyruvate kinase M2 (PKM2) is a glycolytic enzyme known to be involved in metabolic reprogramming and gene transcription in many immune cell types, its role in neutrophils remains poorly understood. Here, we report that PKM2 regulates ROS production and microbial killing by neutrophils. Zymosan-activated neutrophils showed increased cytoplasmic expression of PKM2. Pharmacological inhibition or genetic deficiency of PKM2 in neutrophils reduced ROS production and Staphylococcus aureus killing in vitro. In addition, this also resulted in phosphoenolpyruvate (PEP) accumulation and decreased dihydroxyacetone phosphate (DHAP) production, which is required for de novo synthesis of diacylglycerol (DAG) from glycolysis. In vivo, PKM2 deficiency in myeloid cells impaired the control of infection with Staphylococcus aureus. Our results fill the gap in the current knowledge of the importance of lower glycolysis for ROS production in neutrophils, highlighting the role of PKM2 in regulating the DHAP and DAG synthesis to promote ROS production in neutrophils. Neutrophil activation has been shown to rely on the pentose phosphate pathway (PPP) for NADPH generation and reactive oxygen species production. In this study, the authors identify a mechanism of neutrophil activation that is independent of the PPP but relies on the glycolytic enzyme pyruvate kinase M2 instead. (AU) | |
| FAPESP's process: | 13/08216-2 - CRID - Center for Research in Inflammatory Diseases |
| Grantee: | Fernando de Queiroz Cunha |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 19/25298-9 - Role of PKM2 in neutrophil metabolism and function |
| Grantee: | Juliana Escher Toller |
| Support Opportunities: | Scholarships abroad - Research Internship - Post-doctor |
| FAPESP's process: | 17/01714-8 - PKM2 contribution to neutrophils' activation in experimental systemic lupus erythematosus onset |
| Grantee: | Juliana Escher Toller |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 20/02207-5 - Inventorying secondary metabolism applying metabolomic strategies: contribution to the Brazilian biodiversity valuation |
| Grantee: | Norberto Peporine Lopes |
| Support Opportunities: | BIOTA-FAPESP Program - Thematic Grants |