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

Schroeder, H; McCarthy, D; Szestak, T; Cook, D A; Taylor, M; Craig, A G; Lawson, C; Lawrence, R A

doi:10.1371/journal.pntd.0005592

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

Schroeder, H; McCarthy, D; Szestak, T; Cook, D A; Taylor, M; Craig, A G; Lawson, C; Lawrence, R A

Authors

H Schroeder

D McCarthy

T Szestak

D A Cook

M Taylor

A G Craig

C Lawson

R A Lawrence

Abstract

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.

Citation

Schroeder, H., McCarthy, D., Szestak, T., Cook, D. A., Taylor, M., Craig, A. G., …Lawrence, R. A. (2017). Brugia malayi microfilariae adhere to human vascular endothelial cells in a C3-dependent manner. PLoS Neglected Tropical Diseases, 11(5), e0005592. https://doi.org/10.1371/journal.pntd.0005592

Journal Article Type	Article
Acceptance Date	May 8, 2017
Publication Date	May 8, 2017
Deposit Date	May 18, 2017
Publicly Available Date	May 18, 2017
Journal	PLOS NEGLECTED TROPICAL DISEASES
Print ISSN	1935-2727
Publisher	Public Library of Science
Peer Reviewed	Peer Reviewed
Volume	11
Issue	5
Pages	e0005592
DOI	https://doi.org/10.1371/journal.pntd.0005592
Public URL	https://rvc-repository.worktribe.com/output/1392022