Journal article
Neutrophil- Leishmania infantum Interaction Induces Neutrophil Extracellular Traps, DAMPs, and Inflammatory Molecule Release
ACS infectious diseases, Vol.11(2), pp.483-492
02/14/2025
DOI: 10.1021/acsinfecdis.4c00820
PMCID: PMC11833875
PMID: 39887021
Abstract
Neutrophils, the first cells to arrive at infection sites, release neutrophil extracellular traps (NETs) comprising nuclear and/or mitochondrial DNA webs decorated with proteins. Similar to other parasites,
induces NET extrusion. However, our understanding of NET formation and neutrophil fate after NET release in a Leishmania infection context is limited. Our study aimed to determine the DNA origin of the NET scaffolds released by human neutrophils in response to chemical or
stimulation. Neutrophils were incubated with PMA, PHA, LPS, or
, followed by DNA and elastase activity quantification; additionally, we evaluated the source of DNA that composes NETs. Neutrophil viability was evaluated by annexin-V/7AAd labeling. Expression of IL6, TNFA, IL10, CXCL1, CXCL8, and FPR1 in response to the
interaction was assessed. Neutrophils incubated with chemicals or
released NETs. However, neutrophils stimulated by the chemicals showed lower viability after 1 h in comparison to neutrophils incubated with parasites. NETs from chemically stimulated neutrophils were mainly composed of nuclear DNA. Conversely, the NET induced by the parasites was of mitochondrial DNA origin and had no leishmanicidal activity. After 4 h of parasite stimulation, neutrophils peak the expression of genes such as IL6, TNFA, CXCL1, CXCL8, and FPR1. Our study demonstrates that neutrophils produce NETs after chemical or
exposure. Although they are not toxic to the parasite, NETs are released as danger signals. These findings support the role of neutrophils in releasing signaling molecules, which influence the inflammatory environment in which the infectious process occurs.
Details
- Title: Subtitle
- Neutrophil- Leishmania infantum Interaction Induces Neutrophil Extracellular Traps, DAMPs, and Inflammatory Molecule Release
- Creators
- Paulo Ricardo Porfírio do Nascimento - Nova Southeastern UniversityCarolina Oliveira Mendes-Aguiar - Instituto Federal do Rio Grande do NorteIngryd Câmara Morais - Instituto Federal do Rio Grande do NorteJoão Firmino Rodrigues Neto - University of Rio Grande and Rio Grande Community CollegeMary E Wilson - University of IowaSelma Maria Bezerra Jerônimo - Instituto Federal do Rio Grande do Norte
- Resource Type
- Journal article
- Publication Details
- ACS infectious diseases, Vol.11(2), pp.483-492
- DOI
- 10.1021/acsinfecdis.4c00820
- PMID
- 39887021
- PMCID
- PMC11833875
- NLM abbreviation
- ACS Infect Dis
- ISSN
- 2373-8227
- eISSN
- 2373-8227
- Publisher
- AMER CHEMICAL SOC
- Grant note
- Brazilian National Institutes of Science and Technology of Tropical Diseases: 465229/2014-0 Brazilian National Council of Research and Technology (CNPq): 406076/2021-9 Coordination for the Improvement of Higher Education Personnel- CAPES: 00x0ma614
Funding This study was supported by a Grant from the Brazilian National Institutes of Science and Technology of Tropical Diseases (#465229/2014-0) and by a grant from Brazilian National Council of Research and Technology (CNPq)- Universal 406076/2021-9.
The Article Processing Charge for the publication of this research was funded by the Coordination for the Improvement of Higher Education Personnel- CAPES (ROR identifier: 00x0ma614). - Language
- English
- Electronic publication date
- 01/31/2025
- Date published
- 02/14/2025
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; International Programs; Epidemiology; Internal Medicine
- Record Identifier
- 9984781374502771
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