Journal article
Mitochondria sense bacterial lactate and drive release of neutrophil extracellular traps
Cell host & microbe, Vol.33(3), pp.341-357.e9
02/20/2025
DOI: 10.1016/j.chom.2025.02.003
PMCID: PMC11955204
PMID: 40020664
Abstract
Neutrophils induce oxidative stress, creating a harsh phagosomal environment. However, Staphylococcus aureus can survive these conditions, requiring neutrophils to deploy mechanisms that sense bacterial persistence. We find that staphylococcal lactate is a metabolic danger signal that triggers neutrophil extracellular trap release (NETosis). Neutrophils coordinate mitochondria in proximity to S. aureus-containing phagosomes, allowing transfer of staphylococcal lactate to mitochondria where it is rapidly converted into pyruvate and causes mitochondrial reactive oxygen species, a precursor to NETosis. Similar results were observed in response to phylogenetically distinct bacteria, implicating lactate accumulation as a broad signal triggering NETosis. Furthermore, patients with systemic lupus erythematosus (SLE) are more susceptible to bacterial infections. We find that SLE neutrophils cannot sense bacterial lactate impairing their capacity to undergo NETosis upon S. aureus infection but initiate aberrant NETosis triggered by apoptotic debris. Thus, neutrophils adapt mitochondria as sensory organelles that detect bacterial metabolic activity and dictate downstream antibacterial processes.
Details
- Title: Subtitle
- Mitochondria sense bacterial lactate and drive release of neutrophil extracellular traps
- Creators
- Ashley D Wise - University of Tennessee at KnoxvilleEden G TenBarge - University of Tennessee at KnoxvilleJessica D C Mendonça - University of Tennessee at KnoxvilleEllie C Mennen - University of Tennessee at KnoxvilleSarah R McDaniel - University of Tennessee at KnoxvilleCallista P Reber - University of Tennessee at KnoxvilleBailey E Holder - University of Tennessee at KnoxvilleMadison L Bunch - University of IowaEva Belevska - University of Tennessee at KnoxvilleMadalyn G Marshall - University of Tennessee at KnoxvilleNicole M Vaccaro - University of Tennessee at KnoxvilleChristian R Blakely - University of Tennessee at KnoxvilleDinesh H Wellawa - University of SaskatchewanJennifer Ferris - University of Tennessee at KnoxvilleJessica R Sheldon - University of SaskatchewanJeffry D Bieber - University of Tennessee Medical CenterJeremiah G Johnson - University of IowaLindsey R Burcham - University of Tennessee at KnoxvilleAndrew J Monteith - University of Tennessee at Knoxville
- Resource Type
- Journal article
- Publication Details
- Cell host & microbe, Vol.33(3), pp.341-357.e9
- DOI
- 10.1016/j.chom.2025.02.003
- PMID
- 40020664
- PMCID
- PMC11955204
- NLM abbreviation
- Cell Host Microbe
- ISSN
- 1934-6069
- eISSN
- 1934-6069
- Publisher
- CELL PRESS
- Grant note
- UTK start-up funds: 1R35GM154838, R01AI166535 UT Human Health and Wellness Research Development ProgramUSask CoM start-up fundsSaskatchewan Health Research Foundation
We thank Eric Skaar, Thomas Vinai, Tammy Kielian, Anthony Richardson, William Beavers, Jason Rosch, and Victor DiRita for providing bacterial strains. We thank the University of Tennessee Advanced Microscopy and Imaging Center and Amit Joshi for providing the confocal microscopes and Jaydeep Kolape for providing technical assistance. We thank the individuals who provided blood and the support staff at UTMC who facilitated the process. We thank Onyx Mitchell and Trixie TenBarge for providing emotional support and members of the Sparer and Donohoe laboratories for providing scientific feedback. This work was supported by UTK start-up funds (to A.J.M.) , 1R35GM154838 (to A.J.M.) , UT Human Health and Wellness Research Development Program (to A.J.M.) , UTK start-up funds (to L.R.B.) , R01AI166535 (to J.G.J.) , USask CoM start-up funds (to J.R.S.) and an Establishment Grant from the Saskatchewan Health Research Foundation (to J.R.S.) .
- Language
- English
- Date published
- 02/20/2025
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984798225602771
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