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Journal of extracellular vesicles
Apr, 2025;14 (4): e70074.

Yersinia pestis Actively Inhibits the Production of Extracellular Vesicles by Human Neutrophils.

Katelyn R Sheneman, Timothy D Cummins, Michael L Merchant, Joshua L Hood, Silvia M Uriarte, Matthew B Lawrenz
Author Information
  1. Katelyn R Sheneman: Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA. ORCID
  2. Timothy D Cummins: Department of Medicine and Proteomics Technology Center, University of Louisville, Louisville, Kentucky, USA. ORCID
  3. Michael L Merchant: Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, USA. ORCID
  4. Joshua L Hood: Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, USA. ORCID
  5. Silvia M Uriarte: Department of Oral Immunology & Infectious Disease, University of Louisville, Louisville, Kentucky, USA. ORCID
  6. Matthew B Lawrenz: Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA. ORCID
PMID: 40240908 DOI: 10.1002/jev2.70074

Abstract

Yersinia pestis is the etiologic agent of the plague. A hallmark of plague is subversion of the host immune response by disrupting host signalling pathways required for inflammation. This non-inflammatory environment permits bacterial colonization and has been shown to be essential for disease manifestation. Previous work has shown that Y. pestis inhibits phagocytosis and degranulation by neutrophils. Manipulation of these key vesicular trafficking pathways suggests that Y. pestis influences extracellular vesicle (EV) secretion, cargo selection, trafficking and/or maturation. Our goals were to define the EV population produced by neutrophils in response to Y. pestis and determine how these vesicles might influence inflammation. Towards these goals, EVs were isolated from human neutrophils infected with Y. pestis or a mutant lacking bacterial effector proteins known to manipulate host cell signalling. Mass spectrometry data revealed that cargoes packaged in EVs isolated from mutant infected cells were enriched with antimicrobial and cytotoxic proteins, contents which differed from uninfected and Y. pestis infected cells. Further, EVs produced in response to Y. pestis lacked inflammatory properties observed in those isolated from neutrophils responding to the mutant. Together, these data demonstrate that Y. pestis actively inhibits the production of antimicrobial EVs produced by neutrophils, likely contributing to immune evasion.

Keywords

Yersinia pestis Yop effectors human neutrophils (hPMNs) plague type 3 secretion system (T3SS)

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Grants

  1. P20GM103436/NIGMS NIH HHS
  2. P20GM113226/NIGMS NIH HHS
  3. P20 GM103436/NIGMS NIH HHS
  4. R01AI148241/National Institute of Allergy and Infectious Diseases
  5. F31AI178999/National Institute of Allergy and Infectious Diseases
  6. R21 AI169423/NIAID NIH HHS
  7. R01 AI178106/NIAID NIH HHS
  8. /Jewish Heritage for Excellence Fund
  9. F31 AI178999/NIAID NIH HHS
  10. R01AI178106/National Institute of Allergy and Infectious Diseases
  11. P20 GM113226/NIGMS NIH HHS
  12. R01 AI148241/NIAID NIH HHS
  13. /University of Louisville Proteomics Technology Center
  14. R21AI169423/National Institute of Allergy and Infectious Diseases

MeSH Term

Humans
Yersinia pestis
Extracellular Vesicles
Neutrophils
Plague
Phagocytosis
Journal Article

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