Human Leukocytes Kill Brugia malayi Microfilariae Independently of DNA-Based Extracellular Trap Release.
BACKGROUND:Wuchereria bancrofti, Brugia malayi and Brugia timori infect over 100 million people worldwide and are the causative agents of lymphatic filariasis. Some parasite carriers are amicrofilaremic whilst others facilitate mosquito-based disease transmission through blood-circulating microfilar...
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ftdoajarticles:oai:doaj.org/article:a9c9978a135c483e93810f3938886800 2023-05-15T15:16:22+02:00 Human Leukocytes Kill Brugia malayi Microfilariae Independently of DNA-Based Extracellular Trap Release. Ciaran J McCoy Barbara J Reaves Steeve Giguère Ruby Coates Balázs Rada Adrian J Wolstenholme 2017-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0005279 https://doaj.org/article/a9c9978a135c483e93810f3938886800 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5234842?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005279 https://doaj.org/article/a9c9978a135c483e93810f3938886800 PLoS Neglected Tropical Diseases, Vol 11, Iss 1, p e0005279 (2017) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2017 ftdoajarticles https://doi.org/10.1371/journal.pntd.0005279 2022-12-31T04:12:28Z BACKGROUND:Wuchereria bancrofti, Brugia malayi and Brugia timori infect over 100 million people worldwide and are the causative agents of lymphatic filariasis. Some parasite carriers are amicrofilaremic whilst others facilitate mosquito-based disease transmission through blood-circulating microfilariae (Mf). Recent findings, obtained largely from animal model systems, suggest that polymorphonuclear leukocytes (PMNs) contribute to parasitic nematode-directed type 2 immune responses. When exposed to certain pathogens PMNs release extracellular traps (NETs) in the form of chromatin loaded with various antimicrobial molecules and proteases. PRINCIPAL FINDINGS:In vitro, PMNs expel large amounts of NETs that capture but do not kill B. malayi Mf. NET morphology was confirmed by fluorescence imaging of worm-NET aggregates labelled with DAPI and antibodies to human neutrophil elastase, myeloperoxidase and citrullinated histone H4. A fluorescent, extracellular DNA release assay was used to quantify and observe Mf induced NETosis over time. Blinded video analyses of PMN-to-worm attachment and worm survival during Mf-leukocyte co-culture demonstrated that DNase treatment eliminates PMN attachment in the absence of serum, autologous serum bolsters both PMN attachment and PMN plus peripheral blood mononuclear cell (PBMC) mediated Mf killing, and serum heat inactivation inhibits both PMN attachment and Mf killing. Despite the effects of heat inactivation, the complement inhibitor compstatin did not impede Mf killing and had little effect on PMN attachment. Both human PMNs and monocytes, but not lymphocytes, are able to kill B. malayi Mf in vitro and NETosis does not significantly contribute to this killing. Leukocytes derived from presumably parasite-naïve U.S. resident donors vary in their ability to kill Mf in vitro, which may reflect the pathological heterogeneity associated with filarial parasitic infections. CONCLUSIONS/SIGNIFICANCE:Human innate immune cells are able to recognize, attach to and kill B. malayi ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 11 1 e0005279 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Ciaran J McCoy Barbara J Reaves Steeve Giguère Ruby Coates Balázs Rada Adrian J Wolstenholme Human Leukocytes Kill Brugia malayi Microfilariae Independently of DNA-Based Extracellular Trap Release. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:Wuchereria bancrofti, Brugia malayi and Brugia timori infect over 100 million people worldwide and are the causative agents of lymphatic filariasis. Some parasite carriers are amicrofilaremic whilst others facilitate mosquito-based disease transmission through blood-circulating microfilariae (Mf). Recent findings, obtained largely from animal model systems, suggest that polymorphonuclear leukocytes (PMNs) contribute to parasitic nematode-directed type 2 immune responses. When exposed to certain pathogens PMNs release extracellular traps (NETs) in the form of chromatin loaded with various antimicrobial molecules and proteases. PRINCIPAL FINDINGS:In vitro, PMNs expel large amounts of NETs that capture but do not kill B. malayi Mf. NET morphology was confirmed by fluorescence imaging of worm-NET aggregates labelled with DAPI and antibodies to human neutrophil elastase, myeloperoxidase and citrullinated histone H4. A fluorescent, extracellular DNA release assay was used to quantify and observe Mf induced NETosis over time. Blinded video analyses of PMN-to-worm attachment and worm survival during Mf-leukocyte co-culture demonstrated that DNase treatment eliminates PMN attachment in the absence of serum, autologous serum bolsters both PMN attachment and PMN plus peripheral blood mononuclear cell (PBMC) mediated Mf killing, and serum heat inactivation inhibits both PMN attachment and Mf killing. Despite the effects of heat inactivation, the complement inhibitor compstatin did not impede Mf killing and had little effect on PMN attachment. Both human PMNs and monocytes, but not lymphocytes, are able to kill B. malayi Mf in vitro and NETosis does not significantly contribute to this killing. Leukocytes derived from presumably parasite-naïve U.S. resident donors vary in their ability to kill Mf in vitro, which may reflect the pathological heterogeneity associated with filarial parasitic infections. CONCLUSIONS/SIGNIFICANCE:Human innate immune cells are able to recognize, attach to and kill B. malayi ... |
format |
Article in Journal/Newspaper |
author |
Ciaran J McCoy Barbara J Reaves Steeve Giguère Ruby Coates Balázs Rada Adrian J Wolstenholme |
author_facet |
Ciaran J McCoy Barbara J Reaves Steeve Giguère Ruby Coates Balázs Rada Adrian J Wolstenholme |
author_sort |
Ciaran J McCoy |
title |
Human Leukocytes Kill Brugia malayi Microfilariae Independently of DNA-Based Extracellular Trap Release. |
title_short |
Human Leukocytes Kill Brugia malayi Microfilariae Independently of DNA-Based Extracellular Trap Release. |
title_full |
Human Leukocytes Kill Brugia malayi Microfilariae Independently of DNA-Based Extracellular Trap Release. |
title_fullStr |
Human Leukocytes Kill Brugia malayi Microfilariae Independently of DNA-Based Extracellular Trap Release. |
title_full_unstemmed |
Human Leukocytes Kill Brugia malayi Microfilariae Independently of DNA-Based Extracellular Trap Release. |
title_sort |
human leukocytes kill brugia malayi microfilariae independently of dna-based extracellular trap release. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2017 |
url |
https://doi.org/10.1371/journal.pntd.0005279 https://doaj.org/article/a9c9978a135c483e93810f3938886800 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 11, Iss 1, p e0005279 (2017) |
op_relation |
http://europepmc.org/articles/PMC5234842?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005279 https://doaj.org/article/a9c9978a135c483e93810f3938886800 |
op_doi |
https://doi.org/10.1371/journal.pntd.0005279 |
container_title |
PLOS Neglected Tropical Diseases |
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11 |
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1 |
container_start_page |
e0005279 |
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1766346647927783424 |