Abstract
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.
Highlights
Soil transmitted helminths have a major impact on both human and animal health
We found that eosinophil granule products affected the transport of Rhodamine 123 (Rh123) that has previously been shown to be mediated by Pgp transporters
Eosinophil granule proteins are stored in a crystalloid structure that can be purified by ultracentrifugation [32]
Summary
Soil transmitted helminths have a major impact on both human and animal health. These parasites are responsible for increased morbidity, mortality and premature birth [1,2,3,4]. While the host immune response against parasitic helminths is highly complex, granulocytes are known to be involved in both the initiation and effector immune response phases [5,6]. These responses are associated with a proliferation of T-helper 2 lymphocytes, plasma cells, eosinophil cells, basophils and mast cells [7,8]. Eosinophils release cationic proteins with significant cytotoxic activity such as the major basic protein, eosinophil peroxidase and eosinophil-derived neurotoxin [10] In this respect, it is expected that successful establishment of the parasite in vivo might require efficient detoxification mechanisms to defend against the host immune response products.
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