Human neutrophil extracellular traps do not impair in vitro Toxoplasma gondii infection.
Abstract: , responsible for causing toxoplasmosis, is a prevalent food and waterborne pathogen worldwide. It commonly infects warm-blooded animals and affects more than a third of the global human population. Once ingested, the parasite enters the host's small intestine and rapidly disseminates throughout the body via the bloodstream, infiltrating various tissues. Leukocyte-driven responses are vital against , with neutrophils playing a dual role: swiftly recruited to infection sites, releasing inflammatory mediators, and serving as a replication hub and Trojan horses, aiding parasite spread. Neutrophils from various hosts release extracellular traps (NETs) against the protozoan. However, gaps persist regarding the mechanisms of NETs production to parasite and their significance in infection control. This study investigates the interplay between human neutrophils and , exploring dynamics, key molecules, and signaling pathways involved in NETs production upon protozoan challenge. Unassigned: Using confocal and electron microscopy, live cell imaging, pharmacological inhibitors, and DNA quantification assays, we find that human neutrophils promptly release both classical and rapid NETs upon pathogen stimulation. The NETs structure exhibits diverse phenotypes over time and is consistently associated with microorganisms. Mechanisms involve neutrophil elastase and peptidylarginine deiminase, along with intracellular calcium signaling and the PI3K pathway. Unexpectedly, human traps do not diminish viability or infectivity, but potentially aid in capturing parasites for subsequent neutrophil phagocytosis and elimination. Unassigned: By revealing NETs formation mechanisms and their nuanced impact on infection dynamics, our findings contribute to broader insights into host-pathogen relationships.
Copyright © 2023 Macedo, Lara, Barbosa, Saraiva, Menna-Barreto and Mariante.
Publication Date: 2023-12-05 PubMed ID: 38115994PubMed Central: PMC10728484DOI: 10.3389/fimmu.2023.1282278Google Scholar: Lookup
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- Journal Article
Summary
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The research article investigates how human neutrophils, a type of immune cell, react to Toxoplasma gondii, a common pathogen that causes toxoplasmosis, and the processes and pathways involved in the production of neutrophil extracellular traps (NETs). However, contrary to expectations, the study finds that these NETs do not reduce the parasite’s viability or infectivity.
Research Summary
- The research is focused on understanding how Toxoplasma gondii, a pathogen that infects a large portion of the global population and causes toxoplasmosis, interacts with human neutrophils (white blood cells) as part of the immune response.
- It is crucial to understand this interaction as the pathogen quickly spreads throughout the body once ingested, necessitating defense reactions from immune cells like leukocytes with neutrophils playing especially significant roles. However, details of the mechanisms of Neutrophil extracellular traps (NETs) production in reaction to the parasite and its implication on infection control remain unclear.
Methodology and Findings
- Various experiments and assays, including confocal and electron microscopy, live cell imaging, pharmacological inhibitors, and DNA quantification, were used to explore the reactions and interactions between the pathogen and human neutrophils.
- Results showed that human neutrophils quickly release two types of NETS when exposed to the pathogen; the structure of which changes over time. The production mechanisms involved elastase and peptidylarginine deiminase, intracellular calcium signaling, and the PI3K pathway.
- Contrary to expectations, these NETs did not reduce the viability or infectivity of Toxoplasma gondii. It was suggested that they might assist in capturing the parasites for neutrophil phagocytosis and elimination.
Conclusion
- The research aids in broadening understanding of host-pathogen interactions by revealing the mechanisms behind NETs formation and its nuanced effect on Toxoplasma gondii infection dynamics.
Cite This Article
APA
Macedo IS, Lara FA, Barbosa HS, Saraiva EM, Menna-Barreto RFS, Mariante RM.
(2023).
Human neutrophil extracellular traps do not impair in vitro Toxoplasma gondii infection.
Front Immunol, 14, 1282278.
https://doi.org/10.3389/fimmu.2023.1282278 Publication
Researcher Affiliations
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil.
- Laboratório de Microbiologia Celular, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil.
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil.
- Laboratório de Imunobiologia das Leishmanioses, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
- Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil.
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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