Human neutrophil extracellular traps do not impair in vitro Toxoplasma gondii infection
IntroductionToxoplasma gondii, 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 rapidl...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1282278/full |
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| author | Isabela S. Macedo Flávio A. Lara Helene S. Barbosa Elvira M. Saraiva Rubem F. S. Menna-Barreto Rafael M. Mariante |
| author_facet | Isabela S. Macedo Flávio A. Lara Helene S. Barbosa Elvira M. Saraiva Rubem F. S. Menna-Barreto Rafael M. Mariante |
| author_sort | Isabela S. Macedo |
| collection | DOAJ |
| description | IntroductionToxoplasma gondii, 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 T. gondii, 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 T. gondii, exploring dynamics, key molecules, and signaling pathways involved in NETs production upon protozoan challenge.Methods and ResultsUsing 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.DiscussionBy revealing NETs formation mechanisms and their nuanced impact on T. gondii infection dynamics, our findings contribute to broader insights into host-pathogen relationships. |
| first_indexed | 2024-03-09T02:57:24Z |
| format | Article |
| id | doaj.art-bfd51f1daad149689e30cf4cdd72ace5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-09T02:57:24Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-bfd51f1daad149689e30cf4cdd72ace52023-12-05T04:23:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-12-011410.3389/fimmu.2023.12822781282278Human neutrophil extracellular traps do not impair in vitro Toxoplasma gondii infectionIsabela S. Macedo0Flávio A. Lara1Helene S. Barbosa2Elvira M. Saraiva3Rubem F. S. Menna-Barreto4Rafael M. Mariante5Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, BrazilLaboratório de Microbiologia Celular, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, BrazilLaboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, BrazilLaboratório de Imunobiologia das Leishmanioses, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilLaboratório de Biologia Celular, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, BrazilLaboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, BrazilIntroductionToxoplasma gondii, 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 T. gondii, 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 T. gondii, exploring dynamics, key molecules, and signaling pathways involved in NETs production upon protozoan challenge.Methods and ResultsUsing 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.DiscussionBy revealing NETs formation mechanisms and their nuanced impact on T. gondii infection dynamics, our findings contribute to broader insights into host-pathogen relationships.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1282278/fullNETToxoplasma gondiihuman neutrophilsclassic/rapid NETsinfectivityviability |
| spellingShingle | Isabela S. Macedo Flávio A. Lara Helene S. Barbosa Elvira M. Saraiva Rubem F. S. Menna-Barreto Rafael M. Mariante Human neutrophil extracellular traps do not impair in vitro Toxoplasma gondii infection Frontiers in Immunology NET Toxoplasma gondii human neutrophils classic/rapid NETs infectivity viability |
| title | Human neutrophil extracellular traps do not impair in vitro Toxoplasma gondii infection |
| title_full | Human neutrophil extracellular traps do not impair in vitro Toxoplasma gondii infection |
| title_fullStr | Human neutrophil extracellular traps do not impair in vitro Toxoplasma gondii infection |
| title_full_unstemmed | Human neutrophil extracellular traps do not impair in vitro Toxoplasma gondii infection |
| title_short | Human neutrophil extracellular traps do not impair in vitro Toxoplasma gondii infection |
| title_sort | human neutrophil extracellular traps do not impair in vitro toxoplasma gondii infection |
| topic | NET Toxoplasma gondii human neutrophils classic/rapid NETs infectivity viability |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1282278/full |
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