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Brugia malayi microfilariae adhere to human vascular endothelial cells in a C3-dependent manner

Brugia malayi causes the human tropical disease, lymphatic filariasis. Microfilariae (Mf) of this nematode live in the bloodstream and are ingested by a feeding mosquito vector. Interestingly, in a remarkable co-evolutionary adaptation, Mf appearance in the peripheral blood follows a circadian perio...

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Autores principales: Schroeder, Jan-Hendrik, McCarthy, David, Szestak, Tadge, Cook, Darren A., Taylor, Mark J., Craig, Alister G., Lawson, Charlotte, Lawrence, Rachel A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436873/
https://www.ncbi.nlm.nih.gov/pubmed/28481947
http://dx.doi.org/10.1371/journal.pntd.0005592
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author Schroeder, Jan-Hendrik
McCarthy, David
Szestak, Tadge
Cook, Darren A.
Taylor, Mark J.
Craig, Alister G.
Lawson, Charlotte
Lawrence, Rachel A.
author_facet Schroeder, Jan-Hendrik
McCarthy, David
Szestak, Tadge
Cook, Darren A.
Taylor, Mark J.
Craig, Alister G.
Lawson, Charlotte
Lawrence, Rachel A.
author_sort Schroeder, Jan-Hendrik
collection PubMed
description Brugia malayi causes the human tropical disease, lymphatic filariasis. Microfilariae (Mf) of this nematode live in the bloodstream and are ingested by a feeding mosquito vector. Interestingly, in a remarkable co-evolutionary adaptation, Mf appearance in the peripheral blood follows a circadian periodicity and reaches a peak when the mosquito is most likely to feed. For the remaining hours, the majority of Mf sequester in the lung capillaries. This circadian phenomenon has been widely reported and is likely to maximise parasite fitness and optimise transmission potential. However, the mechanism of Mf sequestration in the lungs remains largely unresolved. In this study, we demonstrate that B. malayi Mf can, directly adhere to vascular endothelial cells under static conditions and under flow conditions, they can bind at high (but not low) flow rates. High flow rates are more likely to be experienced diurnally. Furthermore, a non-periodic nematode adheres less efficiently to endothelial cells. Strikingly C3, the central component of complement, plays a crucial role in the adherence interaction. These novel results show that microfilariae have the ability to bind to endothelial cells, which may explain their sequestration in the lungs, and this binding is increased in the presence of inflammatory mediators.
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spelling pubmed-54368732017-05-26 Brugia malayi microfilariae adhere to human vascular endothelial cells in a C3-dependent manner Schroeder, Jan-Hendrik McCarthy, David Szestak, Tadge Cook, Darren A. Taylor, Mark J. Craig, Alister G. Lawson, Charlotte Lawrence, Rachel A. PLoS Negl Trop Dis Research Article Brugia malayi causes the human tropical disease, lymphatic filariasis. Microfilariae (Mf) of this nematode live in the bloodstream and are ingested by a feeding mosquito vector. Interestingly, in a remarkable co-evolutionary adaptation, Mf appearance in the peripheral blood follows a circadian periodicity and reaches a peak when the mosquito is most likely to feed. For the remaining hours, the majority of Mf sequester in the lung capillaries. This circadian phenomenon has been widely reported and is likely to maximise parasite fitness and optimise transmission potential. However, the mechanism of Mf sequestration in the lungs remains largely unresolved. In this study, we demonstrate that B. malayi Mf can, directly adhere to vascular endothelial cells under static conditions and under flow conditions, they can bind at high (but not low) flow rates. High flow rates are more likely to be experienced diurnally. Furthermore, a non-periodic nematode adheres less efficiently to endothelial cells. Strikingly C3, the central component of complement, plays a crucial role in the adherence interaction. These novel results show that microfilariae have the ability to bind to endothelial cells, which may explain their sequestration in the lungs, and this binding is increased in the presence of inflammatory mediators. Public Library of Science 2017-05-08 /pmc/articles/PMC5436873/ /pubmed/28481947 http://dx.doi.org/10.1371/journal.pntd.0005592 Text en © 2017 Schroeder et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Schroeder, Jan-Hendrik
McCarthy, David
Szestak, Tadge
Cook, Darren A.
Taylor, Mark J.
Craig, Alister G.
Lawson, Charlotte
Lawrence, Rachel A.
Brugia malayi microfilariae adhere to human vascular endothelial cells in a C3-dependent manner
title Brugia malayi microfilariae adhere to human vascular endothelial cells in a C3-dependent manner
title_full Brugia malayi microfilariae adhere to human vascular endothelial cells in a C3-dependent manner
title_fullStr Brugia malayi microfilariae adhere to human vascular endothelial cells in a C3-dependent manner
title_full_unstemmed Brugia malayi microfilariae adhere to human vascular endothelial cells in a C3-dependent manner
title_short Brugia malayi microfilariae adhere to human vascular endothelial cells in a C3-dependent manner
title_sort brugia malayi microfilariae adhere to human vascular endothelial cells in a c3-dependent manner
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436873/
https://www.ncbi.nlm.nih.gov/pubmed/28481947
http://dx.doi.org/10.1371/journal.pntd.0005592
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