Biology Reference
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guinea-pigs considered resistant due to previous exposure to A. suum.
74,75
Therefore, since WS are associated with trapped larvae and are more
abundant in resistant animals, the liver has been consistently identified as
a key site in the immobilization of migrating larvae in mice,
39,59,76
e
78
guinea-pigs,
79,80
and rabbits.
81
Subsequently, we used the previously described Ascaris
53
mouse model
system to explore the significance of inflammatory processes within the
murine lung (utilizing the leucocyte population in bronchalveoloar lavage
(BAL) fluid and lung histopathology.
60
We concluded that the pulmonary
responses reflected larval intensity, intense responses being associated
with high worm burdens rather than with low worm burdens (which
might have provided support for their involvement in host-protective
immunity) and hence we concluded that the inflammatory response
was not prominently involved in primary protection of mice to Ascaris
infection in the lungs. However, as suggested by Cooper and colleagues,
69
the intensity of the response to this stage may have consequences for
subsequent adult worm infections in hosts that enable the worms to
complete their maturation (i.e. humans and pigs for A. lumbricoides and
A. suum, respectively).
The lack of support for a pulmonary mechanism of resistance led us to
revisit the idea that resistance operates at the level of the liver. We focused
on the possibility that a hepatic or post-hepatic factor, which varies
between the susceptible and resistant mouse strain, comes into play
rapidly within 4 days of infection, and is non-T cell or MHC haplotype
dependent, may play a critical role in successful/unsuccessful tissue
migration. A study of the comparative histopathological hepatic inflam-
matory response in C57BL/6j and CBA/Ca mice revealed an important
difference between the two strains.
68
In resistant CBA mice, the most
pronounced response occurred on day 4 post-infection, this coinciding
with the migration of larvae from the liver to the lungs. In contrast, the
most severe inflammatory response that we detected in susceptible
C57BL/6j mice occurred on day 6 post-infection when the majority of the
larvae are known to have already successfully migrated to the lungs. We
concluded that CBA mice handle the parasitic insult more effectively and
economically in terms of an earlier response that restricts the degree of
larval invasion at the liver stage, and effecting a more rapid tissue
recovery without triggering additional inflammation.
68
Significantly,
earlier work on guinea-pigs had identified day 4 as an important time-
point with respect to encapsulation by inflammatory cells in immu-
nized animals with an associated reduction in larval numbers noted in the
lungs.
82,83
Perhaps the most intriguing aspect of all these experiments,
and as yet still not explained, is that the rapid inflammatory response in
the livers of resistant animals must be innately driven and is non-T cell or
MHC haplotype dependent.
