Haemonchus contortus P-glycoproteins interact with host eosinophil granules: a novel insight into the role of ABC transporters in host-parasite interaction.
Eosinophils are one of the major mammalian effector cells encountered by helminths during infection. In the present study, we investigated the effects of eosinophil granule exposure on the sheep parasitic nematode Haemonchus contortus as a model. H. contortus eggs exposed to eosinophil granule products showed increased rhodamine 123 efflux and this effect was not due to loss of egg integrity. Rh123 is known to be a specific P-glycoprotein (Pgp) substrate and led to the hypothesis that in addition to their critical role in xenobiotic resistance, helminth ABC transporters such as Pgp may also be involved in the detoxification of host cytotoxic products. We showed by quantitative RT-PCR that, among nine different H. contortus Pgp genes, Hco-pgp-3, Hco-pgp-9.2, Hco-pgp-11 and, Hco-pgp-16 were specifically up-regulated in parasitic life stages suggesting a potential involvement of these Pgps in the detoxification of eosinophil granule products. Using exsheathed L3 larvae that mimic the first life stage in contact with the host, we demonstrated that eosinophil granules induced a dose dependent overexpression of Hco-pgp-3 and the closely related Hco-pgp-16. Taken together, our results provide the first evidence that a subset of helminth Pgps interact with, and could be involved in the detoxification of, host products. This opens the way for further studies aiming to explore the role of helminth Pgps in the host-parasite interaction, including evasion of the host immune response.
INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France ; Université François Rabelais de Tours, UMR1282 Infectiologie et Santé Publique, Tours, France.
Mohamed
M
Issouf
INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France ; Université François Rabelais de Tours, UMR1282 Infectiologie et Santé Publique, Tours, France.
Fabrice
F
Guégnard
INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France ; Université François Rabelais de Tours, UMR1282 Infectiologie et Santé Publique, Tours, France.
Christine
C
Koch
INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France ; Université François Rabelais de Tours, UMR1282 Infectiologie et Santé Publique, Tours, France.
Yves
Y
Le Vern
INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France ; Université François Rabelais de Tours, UMR1282 Infectiologie et Santé Publique, Tours, France.
Alexandra
A
Blanchard-Letort
Institute of Parasitology, McGill University, Quebec, Canada.
Hua
H
Che
INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France ; Institute of Parasitology, McGill University, Quebec, Canada.
Robin N
RN
Beech
INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France ; Université François Rabelais de Tours, UMR1282 Infectiologie et Santé Publique, Tours, France.
Dominique
D
Kerboeuf
INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France ; Université François Rabelais de Tours, UMR1282 Infectiologie et Santé Publique, Tours, France.
Cedric
C
Neveu
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003594:Cytoplasmic Granules / Q000378:metabolism*; D018509:DNA, Helminth / Q000235:genetics; D004804:Eosinophils / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006188:Haemonchiasis / Q000235:genetics / Q000378:metabolism* / Q000469:parasitology; D006189:Haemonchus / Q000502:physiology*; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D006790:Host-Parasite Interactions / Q000502:physiology*; D008297:Male; D010802:Phylogeny; D060888:Real-Time Polymerase Chain Reaction; D012756:Sheep
D018435:ATP Binding Cassette Transporter, Subfamily B; D018509:DNA, Helminth; D015801:Helminth Proteins