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  4. Antibodies Trap Tissue Migrating Helminth Larvae and Prevent Tissue Damage by Driving IL-4Rα-Independent Alternative Differentiation of Macrophages
 
research article

Antibodies Trap Tissue Migrating Helminth Larvae and Prevent Tissue Damage by Driving IL-4Rα-Independent Alternative Differentiation of Macrophages

Esser-von Bieren, Julia  
•
Mosconi, Ilaria  
•
Guiet, Romain  
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2013
Plos Pathogens

Approximately one-third of the world's population suffers from chronic helminth infections with no effective vaccines currently available. Antibodies and alternatively activated macrophages (AAM) form crucial components of protective immunity against challenge infections with intestinal helminths. However, the mechanisms by which antibodies target these large multi-cellular parasites remain obscure. Alternative activation of macrophages during helminth infection has been linked to signaling through the IL-4 receptor alpha chain (IL-4Rα), but the potential effects of antibodies on macrophage differentiation have not been explored. We demonstrate that helminth-specific antibodies induce the rapid trapping of tissue migrating helminth larvae and prevent tissue necrosis following challenge infection with the natural murine parasite Heligmosomoides polygyrus bakeri (Hp). Mice lacking antibodies (JH−/−) or activating Fc receptors (FcRγ−/−) harbored highly motile larvae, developed extensive tissue damage and accumulated less Arginase-1 expressing macrophages around the larvae. Moreover, Hp-specific antibodies induced FcRγ- and complement-dependent adherence of macrophages to larvae in vitro, resulting in complete larval immobilization. Antibodies together with helminth larvae reprogrammed macrophages to express wound-healing associated genes, including Arginase-1, and the Arginase-1 product L-ornithine directly impaired larval motility. Antibody-induced expression of Arginase-1 in vitro and in vivo occurred independently of IL-4Rα signaling. In summary, we present a novel IL-4Rα-independent mechanism of alternative macrophage activation that is antibody-dependent and which both mediates anti-helminth immunity and prevents tissue disruption caused by migrating larvae.

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Type
research article
DOI
10.1371/journal.ppat.1003771
Web of Science ID

WOS:000330386900031

Author(s)
Esser-von Bieren, Julia  
Mosconi, Ilaria  
Guiet, Romain  
Piersigilli, Alessandra
Volpe, Beatrice  
Chen, Fei
Gause, William C.
Seitz, Arne  
Verbeek, J. Sjef
Harris, Nicola  
Date Issued

2013

Publisher

Public Library of Science

Published in
Plos Pathogens
Volume

9

Issue

11

Article Number

e1003771

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPHARRIS  
PTBIOP  
Available on Infoscience
December 7, 2013
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/97485
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