Cargando…
Bovine Polymorphonuclear Neutrophils Cast Neutrophil Extracellular Traps against the Abortive Parasite Neospora caninum
Neospora caninum represents a relevant apicomplexan parasite causing severe reproductive disorders in cattle worldwide. Neutrophil extracellular trap (NET) generation was recently described as an efficient defense mechanism of polymorphonuclear neutrophils (PMN) acting against different parasites. I...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447047/ https://www.ncbi.nlm.nih.gov/pubmed/28611772 http://dx.doi.org/10.3389/fimmu.2017.00606 |
_version_ | 1783239228829728768 |
---|---|
author | Villagra-Blanco, Rodolfo Silva, Liliana M. R. Muñoz-Caro, Tamara Yang, Zhengtao Li, Jianhua Gärtner, Ulrich Taubert, Anja Zhang, Xichen Hermosilla, Carlos |
author_facet | Villagra-Blanco, Rodolfo Silva, Liliana M. R. Muñoz-Caro, Tamara Yang, Zhengtao Li, Jianhua Gärtner, Ulrich Taubert, Anja Zhang, Xichen Hermosilla, Carlos |
author_sort | Villagra-Blanco, Rodolfo |
collection | PubMed |
description | Neospora caninum represents a relevant apicomplexan parasite causing severe reproductive disorders in cattle worldwide. Neutrophil extracellular trap (NET) generation was recently described as an efficient defense mechanism of polymorphonuclear neutrophils (PMN) acting against different parasites. In vitro interactions of bovine PMN with N. caninum were analyzed at different ratios and time spans. Extracellular DNA staining was used to illustrate the typical molecules of NETs [i.e., histones (H3), neutrophil elastase (NE), myeloperoxidase (MPO), pentraxin] via antibody-based immunofluorescence analyses. Functional inhibitor treatments were applied to reveal the role of several enzymes [NADPH oxidase (NOX), NE, MPO, PAD4], ATP-dependent P2Y2 receptor, store-operated Ca(++)entry (SOCE), CD11b receptor, ERK1/2- and p38 MAPK-mediated signaling pathway in tachyzoite-triggered NETosis. N. caninum tachyzoites triggered NETosis in a time- and dose-dependent manner. Scanning electron microscopy analyses revealed NET structures being released by bovine PMN and entrapping tachyzoites. N. caninum-induced NET formation was found not to be NOX-, NE-, MPO-, PAD4-, ERK1/2-, and p38 MAP kinase-dependent process since inhibition of these enzymes led to a slight decrease of NET formation. CD11b was also identified as a neutrophil receptor being involved in NETosis. Furthermore, N. caninum-triggered NETosis depends on Ca(++) influx as well as neutrophil metabolism since both the inhibition of SOCE and of P2Y2-mediated ATP uptake diminished NET formation. Host cell invasion assays indicated that PMN-derived NETosis hampered tachyzoites from active host cell invasion, thereby inhibiting further intracellular replication. NET formation represents an early and effective mechanism of response of the innate immune system, which might reduce initial infection rates during the acute phase of cattle neosporosis. |
format | Online Article Text |
id | pubmed-5447047 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-54470472017-06-13 Bovine Polymorphonuclear Neutrophils Cast Neutrophil Extracellular Traps against the Abortive Parasite Neospora caninum Villagra-Blanco, Rodolfo Silva, Liliana M. R. Muñoz-Caro, Tamara Yang, Zhengtao Li, Jianhua Gärtner, Ulrich Taubert, Anja Zhang, Xichen Hermosilla, Carlos Front Immunol Immunology Neospora caninum represents a relevant apicomplexan parasite causing severe reproductive disorders in cattle worldwide. Neutrophil extracellular trap (NET) generation was recently described as an efficient defense mechanism of polymorphonuclear neutrophils (PMN) acting against different parasites. In vitro interactions of bovine PMN with N. caninum were analyzed at different ratios and time spans. Extracellular DNA staining was used to illustrate the typical molecules of NETs [i.e., histones (H3), neutrophil elastase (NE), myeloperoxidase (MPO), pentraxin] via antibody-based immunofluorescence analyses. Functional inhibitor treatments were applied to reveal the role of several enzymes [NADPH oxidase (NOX), NE, MPO, PAD4], ATP-dependent P2Y2 receptor, store-operated Ca(++)entry (SOCE), CD11b receptor, ERK1/2- and p38 MAPK-mediated signaling pathway in tachyzoite-triggered NETosis. N. caninum tachyzoites triggered NETosis in a time- and dose-dependent manner. Scanning electron microscopy analyses revealed NET structures being released by bovine PMN and entrapping tachyzoites. N. caninum-induced NET formation was found not to be NOX-, NE-, MPO-, PAD4-, ERK1/2-, and p38 MAP kinase-dependent process since inhibition of these enzymes led to a slight decrease of NET formation. CD11b was also identified as a neutrophil receptor being involved in NETosis. Furthermore, N. caninum-triggered NETosis depends on Ca(++) influx as well as neutrophil metabolism since both the inhibition of SOCE and of P2Y2-mediated ATP uptake diminished NET formation. Host cell invasion assays indicated that PMN-derived NETosis hampered tachyzoites from active host cell invasion, thereby inhibiting further intracellular replication. NET formation represents an early and effective mechanism of response of the innate immune system, which might reduce initial infection rates during the acute phase of cattle neosporosis. Frontiers Media S.A. 2017-05-29 /pmc/articles/PMC5447047/ /pubmed/28611772 http://dx.doi.org/10.3389/fimmu.2017.00606 Text en Copyright © 2017 Villagra-Blanco, Silva, Muñoz-Caro, Yang, Li, Gärtner, Taubert, Zhang and Hermosilla. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Villagra-Blanco, Rodolfo Silva, Liliana M. R. Muñoz-Caro, Tamara Yang, Zhengtao Li, Jianhua Gärtner, Ulrich Taubert, Anja Zhang, Xichen Hermosilla, Carlos Bovine Polymorphonuclear Neutrophils Cast Neutrophil Extracellular Traps against the Abortive Parasite Neospora caninum |
title | Bovine Polymorphonuclear Neutrophils Cast Neutrophil Extracellular Traps against the Abortive Parasite Neospora caninum |
title_full | Bovine Polymorphonuclear Neutrophils Cast Neutrophil Extracellular Traps against the Abortive Parasite Neospora caninum |
title_fullStr | Bovine Polymorphonuclear Neutrophils Cast Neutrophil Extracellular Traps against the Abortive Parasite Neospora caninum |
title_full_unstemmed | Bovine Polymorphonuclear Neutrophils Cast Neutrophil Extracellular Traps against the Abortive Parasite Neospora caninum |
title_short | Bovine Polymorphonuclear Neutrophils Cast Neutrophil Extracellular Traps against the Abortive Parasite Neospora caninum |
title_sort | bovine polymorphonuclear neutrophils cast neutrophil extracellular traps against the abortive parasite neospora caninum |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447047/ https://www.ncbi.nlm.nih.gov/pubmed/28611772 http://dx.doi.org/10.3389/fimmu.2017.00606 |
work_keys_str_mv | AT villagrablancorodolfo bovinepolymorphonuclearneutrophilscastneutrophilextracellulartrapsagainsttheabortiveparasiteneosporacaninum AT silvalilianamr bovinepolymorphonuclearneutrophilscastneutrophilextracellulartrapsagainsttheabortiveparasiteneosporacaninum AT munozcarotamara bovinepolymorphonuclearneutrophilscastneutrophilextracellulartrapsagainsttheabortiveparasiteneosporacaninum AT yangzhengtao bovinepolymorphonuclearneutrophilscastneutrophilextracellulartrapsagainsttheabortiveparasiteneosporacaninum AT lijianhua bovinepolymorphonuclearneutrophilscastneutrophilextracellulartrapsagainsttheabortiveparasiteneosporacaninum AT gartnerulrich bovinepolymorphonuclearneutrophilscastneutrophilextracellulartrapsagainsttheabortiveparasiteneosporacaninum AT taubertanja bovinepolymorphonuclearneutrophilscastneutrophilextracellulartrapsagainsttheabortiveparasiteneosporacaninum AT zhangxichen bovinepolymorphonuclearneutrophilscastneutrophilextracellulartrapsagainsttheabortiveparasiteneosporacaninum AT hermosillacarlos bovinepolymorphonuclearneutrophilscastneutrophilextracellulartrapsagainsttheabortiveparasiteneosporacaninum |