TES proteins inhibit serum-mediated adherence of leucocytes to N. brasiliensis L3 in
vitro, most probably by inhibiting or consuming complement. However, our most important observations have come from examining the impact of TES when added to N. brasiliensis L3 immediately prior to inoculation. Again, TES does not inhibit the recruitment of eosinophils and neutrophils into the site of injection, but does greatly increase the number of larvae able to migrate to the lungs in otherwise highly resistant IL-5 Tg hosts (139). As primary resistance Doxorubicin mw to N. brasiliensis in IL-5 Tg mice is most probably due to the actions of eosinophils, it seems likely that TES interferes with eosinophil function and this may also apply in T. canis infections of mice, dogs and others host species. Alex Loukas (James Cook University, Cairns) when with Rick Maizels and his colleagues at the University of Edinburgh showed that TES consists of at least 20 proteins, with 32 and 120 kDa proteins being most abundant (140). Some of these proteins have intriguing similarities to host proteins with immunological functions. More detailed analysis of these products using modern proteomics technology is now warranted. Ideally, the in vivo effects of TES proteins in the N. brasiliensis-IL-5 Tg model will also be tracked to a single protein. Most immunological studies of intestinal nematodes in mice have focused on expulsion of adult Lck worms
from the gut. It is surprising that so little interest has been shown in resistance during the pre-lung phase of infection, especially because the phenomenon was described many years ago in mice check details exposed to repeated infections with N. brasiliensis (141). Similarly, innate immunity or resistance in the early stages of primary infections are not often explored, except in the context of priming of adaptive immunity. Where parasites enter via the skin, a localized immune response at the site of entry may prevent or limit ongoing primary and secondary infections. This is evident with the
nematodes N. brasiliensis and S. ratti and with trematodes of the genus Schistosoma, but has yet to be demonstrated with hookworms and S. stercoralis. Whilst such responses may be associated with localized pathology, this might be sufficiently limited to cause only transient pathology and discomfort. In contrast, an intense reaction in the lungs might cause severe and possibly fatal collateral damage. Immunity in the skin and pre-lung phases of infection is therefore worthy of further investigation. What might represent a protective response in one anatomical site may not be essential in another and so it is important to consider each of the different stages of migration for tissue-invasive parasites. Adult worms of most intestinal parasite species are likely to be relatively resistant to immunological attack in the gastrointestinal tract.