Human dendritic cell sequestration onto the Necator americanus larval sheath during ex-sheathing: a possible mechanism for immune privilege

Despite the profound health implications of Necator americanus (N. americanus) infection in humans, many aspects of its interaction with the host immune system are poorly understood. Here we investigated the early events at the interface of N. americanus larvae (L3) and human dendritic cells (DCs)....

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Main Authors: Hassan, A., Pritchard, D.I., Ghaemmaghami, A.M.
Format: Article
Published: Cambridge University Press 2018
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Online Access:https://eprints.nottingham.ac.uk/49661/
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author Hassan, A.
Pritchard, D.I.
Ghaemmaghami, A.M.
author_facet Hassan, A.
Pritchard, D.I.
Ghaemmaghami, A.M.
author_sort Hassan, A.
building Nottingham Research Data Repository
collection Online Access
description Despite the profound health implications of Necator americanus (N. americanus) infection in humans, many aspects of its interaction with the host immune system are poorly understood. Here we investigated the early events at the interface of N. americanus larvae (L3) and human dendritic cells (DCs). Our data show that co-culturing DCs and the larvae triggers ex-sheathing of hookworms rapidly where a majority of DCs are sequestered onto the larval sheath allowing the ex-sheathed larvae to migrate away unchallenged. Intriguingly, DCs show negligible interaction with the ex-sheathed larvae, alluding to differences between the surface chemistry of the larva and its sheath. Furthermore, blocking of two key C-type lectin receptors on DC surface (i.e. DC-SIGN and mannose receptor) resulted in inhibition of ex-sheathing process and DC sequestration, highlighting the importance of C-type lectins on DCs in the induction of the ex-sheathing. Analyses of DC phenotype and cytokine profile after co-culture with the N. americanus larvae showed an immature phenotype as evidenced by the low expression of the maturation markers and cytokines. These data provide new insights into early events at the interface of human DCs and N. americanus larvae and could explain how L3 evade immune recognition upon initial interaction with DCs.
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spelling nottingham-496612020-05-04T19:33:08Z https://eprints.nottingham.ac.uk/49661/ Human dendritic cell sequestration onto the Necator americanus larval sheath during ex-sheathing: a possible mechanism for immune privilege Hassan, A. Pritchard, D.I. Ghaemmaghami, A.M. Despite the profound health implications of Necator americanus (N. americanus) infection in humans, many aspects of its interaction with the host immune system are poorly understood. Here we investigated the early events at the interface of N. americanus larvae (L3) and human dendritic cells (DCs). Our data show that co-culturing DCs and the larvae triggers ex-sheathing of hookworms rapidly where a majority of DCs are sequestered onto the larval sheath allowing the ex-sheathed larvae to migrate away unchallenged. Intriguingly, DCs show negligible interaction with the ex-sheathed larvae, alluding to differences between the surface chemistry of the larva and its sheath. Furthermore, blocking of two key C-type lectin receptors on DC surface (i.e. DC-SIGN and mannose receptor) resulted in inhibition of ex-sheathing process and DC sequestration, highlighting the importance of C-type lectins on DCs in the induction of the ex-sheathing. Analyses of DC phenotype and cytokine profile after co-culture with the N. americanus larvae showed an immature phenotype as evidenced by the low expression of the maturation markers and cytokines. These data provide new insights into early events at the interface of human DCs and N. americanus larvae and could explain how L3 evade immune recognition upon initial interaction with DCs. Cambridge University Press 2018-08 Article PeerReviewed Hassan, A., Pritchard, D.I. and Ghaemmaghami, A.M. (2018) Human dendritic cell sequestration onto the Necator americanus larval sheath during ex-sheathing: a possible mechanism for immune privilege. Parasitology, 145 (9). pp. 1183-1190. ISSN 0031-1820 Necator americanus dendritic cells larval sheath exsheathment C-type lectin receptors mannose receptor immune modulation immune evasion hookworm https://www.cambridge.org/core/journals/parasitology/article/human-dendritic-cell-sequestration-onto-the-necator-americanus-larval-sheath-during-exsheathing-a-possible-mechanism-for-immune-privilege/59F251EF5B7193788F2DB9CE31079C36 doi:10.1017/S0031182018000136 doi:10.1017/S0031182018000136
spellingShingle Necator americanus
dendritic cells
larval sheath
exsheathment
C-type lectin receptors
mannose receptor
immune modulation
immune evasion
hookworm
Hassan, A.
Pritchard, D.I.
Ghaemmaghami, A.M.
Human dendritic cell sequestration onto the Necator americanus larval sheath during ex-sheathing: a possible mechanism for immune privilege
title Human dendritic cell sequestration onto the Necator americanus larval sheath during ex-sheathing: a possible mechanism for immune privilege
title_full Human dendritic cell sequestration onto the Necator americanus larval sheath during ex-sheathing: a possible mechanism for immune privilege
title_fullStr Human dendritic cell sequestration onto the Necator americanus larval sheath during ex-sheathing: a possible mechanism for immune privilege
title_full_unstemmed Human dendritic cell sequestration onto the Necator americanus larval sheath during ex-sheathing: a possible mechanism for immune privilege
title_short Human dendritic cell sequestration onto the Necator americanus larval sheath during ex-sheathing: a possible mechanism for immune privilege
title_sort human dendritic cell sequestration onto the necator americanus larval sheath during ex-sheathing: a possible mechanism for immune privilege
topic Necator americanus
dendritic cells
larval sheath
exsheathment
C-type lectin receptors
mannose receptor
immune modulation
immune evasion
hookworm
url https://eprints.nottingham.ac.uk/49661/
https://eprints.nottingham.ac.uk/49661/
https://eprints.nottingham.ac.uk/49661/