Biology Reference
In-Depth Information
FUTURE DIRECTIONS
Evidence has now accumulated to confirm that selective phases of
infection and their impact, specifically the role of the liver migratory
phase, is tractable within a murine model of ascariasis,
29,57
and the
effective hepatic response observed in the resistant CBA/Ca mice can be
further dissected.
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The liver is an important regulator of the systemic
innate immune response. Hepatocytes are the primary synthesizers of all
acute phase proteins (APPs), numerous soluble pathogen recognition
receptors (PRRs), and 80
90% of complement components.
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While
hepatocytes play a key role in the biosynthesis of mediators of the innate
immune system, principal cells of innate immunity are also resident in the
liver
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and the liver has been described as “an organ with predominant
innate immunity.”
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The liver's resident monocytes are macrophage-like
cells, known as Kupffer cells, accounting for 80
e
90% of the total pop-
ulation of fixed tissue macrophages in the body. Kupffer cells are localized
in the liver sinusoids and therefore they are the first hepatic cells to be
exposed to the antigens carried to the liver from the GI tract. It will be
interesting to determine clearly which of these signals for the initiation of
the innate response leading to encapsulation is absent in susceptible
strains and which in particular drive the more intense host-protective
response of resistant animals.
Jungersen et al.
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recognized the importance of assessing the immu-
nological response to A. suum infection at the site at which immunity is
manifested. The lymphocyte population which recognized antigens in
his model system was dependent upon the draining area of the lymph
nodes that were assessed, each of which may be exposed to different
stage-specific antigens
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associated with the presence of larvae in the
surrounding organs or may be dependent upon or constrained by the
effector mechanisms of the immune response that operate in that partic-
ular organ. In our system, conventional T helper cells are unlikely to be
driving the primary response that limits infection in the livers in resistant
strains of mice, but clearly an innate response is involved. Therefore, we
suggest that an investigation of the local production of selected hepatic
cytokines as well as expansion of particular cell populations at certain
key days post-infection in the susceptible and resistant strain of mice
would be a useful line of enquiry, given the differential hepatic inflam-
matory response observed between strains. Crucial to the understanding
of primary resistance, and its failure in susceptible strains of mice, is the
identification of the cells that are primarily responsible for actually driving
this innate inflammatory response, and of the spectrum of cytokines that
they must secrete to marshal host resistance to liver stage larvae.
The mouse model of larval ascariasis could also be used to explore
potential differences between A. lumbricoides and A. suum with respect to
e
