Biology Reference
In-Depth Information
Hepatopulmonary Migration of Larval Stages
Ascaris larvae undertake an extensive migration through their host's
body before they establish as adults in the small intestine. Following the
ingestion of infective eggs and their gastric passage, third-stage larvae
(L3s) 80 emerge from the hatched eggs in the intestine and penetrate the
intestinal wall; they then undergo, via the bloodstream, an arduous
hepatopulmonary migration. The complexity of this migration coin-
cides with important developmental changes in the nematode. 1 Clearly,
this migration requires tightly and rapidly regulated transcriptional
changes in the parasite. We explored this aspect by characterizing the
transcription profiles of infective L3s (from eggs), L3s from the liver or
lungs of the host, and L4s from the small intestine. Peptidases ( n
87) are
significantly enriched in either or both of the migrating L3s (from liver or
lungs). Conspicuous among them are transcripts encoding secreted
peptidases of various families (e.g. C1/C2, M1, M12, S9, and S33), which
have known roles in tissue penetration and degradation during feeding
and/or migration in various helminths, 60 implying a significant role in
Ascaris larvae. Considering the complex nature of migration to and
through specific tissues and organs, with transitions being critical for
parasite development, a key role for molecules associated with chemo-
sensory pathways is highly likely. Such molecules have been studied
extensively in C. elegans , 81 with numerous homologues being identified
in larval transcripts in our study. 11 With few exceptions, all of these
homologues relate to olfactory chemosensation linked to volatile
compounds (e.g. alcohols, aldehydes or ketones), suggesting that the
olfactory detection of molecular gradients is central to the navigation of
A. suum larvae during migration. Lastly, considering the substantial host
attack against migrating Ascaris larvae, ES proteins likely play crucial
roles in immune modulation and/or evasion during hepatopulmonary
migration. This hypothesis is supported by the abundant transcription
linked to orthologues of Bm - alt-1 , Bm - cpi-2 ,and mif-4 in the larval stages
of A. suum , particularly migrating L3s. Collectively, these data shed
significant light on the molecular biology of a crucial component of the
Ascaris life-cycle and will provide an important foundation for future
research into the immunobiology and developmental processes of
A. suum .
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Prediction and Prioritization of Drug Targets
A major challenge in the treatment and control of the world's major
neglected helminths is the limited arsenal of drugs available for their
control. Presently, the control of ascariasis in humans is almost exclu-
sively dependent upon oral dosage with albendanzole/mebendazole. 82
The main advantage of using these compounds, in addition to their
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