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In-Depth Information
comparability between groups. Despite this, it was also established that
resistance in resistant strains of mice did not depend on Tcells, since nude
athymic strains on resistant backgrounds resisted infection just as well as
the wild-type parental strains and was not MHC haplotype dependent.
59
Moreover, much later Lewis et al.
60
found that even treatment with the
highly anti-inflammatory and immunodepressive steroid cortisone made
no impact on the capacity of resistant strains to impair larval migration to
the lungs.
Prior to this, Kennedy and Qureshi
61
and Tomlinson et al.
62
had
concluded that Ascaris in the mouse was a useful model for under-
standing genetic control of the immune repertoire to defined antigens of
the parasite in relation to selective immune responses to antigens of
Ascaris in infected humans (see Chapter 3).
63
e
65
These studies showed
that there was sequential recognition of antigens with time after infec-
tion,
62,66
but concentrated on antibody produced once the immune
response was mature, and hence days after the worm burdens would
have declined to zero. Hence, they did not focus on the critical time when
larvae were still present in the host and still migrating, and when effective
resistance might be expected to operate. It is unlikely therefore that the
antibody responses they described played any significant role in host-
protective immunity to the larval migratory stage of A. suum infection
in their genetically high responder mouse strains.
In an Ascaris mouse model, comprising a susceptible and resistant
strain, a significant reduction in body weight was observed in mice that
received higher doses of Ascaris ova indicating that larval migration and
accumulation of larvae in the lungs has a significant impact upon host
body condition even in abnormal hosts that sustain only the migratory
and tissue-resident phase of infection.
67
After optimization of the methodologies for infection and recovery,
and having compared a panel of nine inbred strains of mice with respect
to larval recovery in the lungs on day 7 post-infection, we identified
a mouse model for susceptibility and resistance to early infection.
53
C57BL/6j mice are consistently highly susceptible to Ascaris larvae in the
lungs, considerably more so than any of the other strains tested, with
worm burdens peaking at day 7 post-infection, in contrast, for example,
to CBA/Ca that remain consistently relatively resistant to lung infection
(see
Figure 5.2
). Therefore, these two mouse strains with highly consis-
tent and diverging larval burdens in their lungs represent the extremes
of the host phenotype displayed in the aggregated distribution and
provide an opportunity to explore the genetic and mechanistic basis of
this difference in response phenotypes.
68
Early events in infection are
likely to play a key role in the determination of an adult worm infection.
More specifically, it has been suggested that pulmonary migration by
Ascaris larvae in humans may create a highly polarized Th2 immune
