Biology Reference
In-Depth Information
co-immunization of mice with OVA and a high molecular weight fraction
inhibited immediate hypersensitivity and DTH to OVA, the proliferation
of lymph node cells to OVA, and Th1/Th2 cytokine and antibody
production.
74
The active component of the high molecular weight fraction
was identified as a 200-kDa protein called PAS-1 that suppressed immune
responses in a dose-dependent fashion.
75
PAS-1 appears to mediate its suppressive effects on cell-mediated
responses and Th1 cytokine responses to heterologous antigens such as
OVA through the production of large amounts of IL-4 and IL-10
72
while
effects on Th2 responses are associated with the elevated production of
IL-10.
76
PAS-1 has been shown to downregulate Th2 responses associated
with the development of asthma in mouse models of A. suum-induced
67
and OVA-induced asthma.
77
PAS-1 can also suppress pro-inflammatory
cytokine responses to LPS-induced inflammation.
72
The suppressive
effect of PAS-1 in OVA-induced asthma has been attributed to the
induction of CD4
þ
þ
regulatory T cells because adoptive transfer of
these cells from PAS-1 immunized mice suppressed allergic responses in
the airways of OVA-immunized and challenged mice.
76
Phosphorylcholine-containing glycosphingolipids from A. suum sup-
pressed IL-12 production by LPS/IFN-
CD25
-stimulated peritoneal macro-
phages and reduced B cell proliferation.
78
Pseudocoelomic body fluid
from adult A. suum worms (ABF) suppressed DTH responses to OVA in
OVA-sensitized mice, an effect on the induction rather than the effector
phase of the immune response, and which was mediated by IL-4 and
IL-10.
79
The potent immunosuppressive effects of A. suum extract on
the host immune response may be related partly to the downregulation
of the antigen-presenting ability of dendritic cells via an IL-10-mediated
mechanism.
80
Overall, these data from experimental animals indicate that some
components of A. suum are potent inducers of inflammatory and allergic
responses while other components have a diverse range of effects in the
modulation of the host immune response that are mediated at least partly
through IL-10-dependent mechanisms.
g
EVIDENCE FOR CLINICALLY RELEVANT
IMMUNE MODULATION BY ASCARIASIS
DURING NATURAL INFECTION
As already discussed, there is evidence that A. lumbricoides infection
modulates the human immune response and, as observed in experimental
animal models, such effects are associated with an increased production
of IL-10 during chronic infections,
10,38
although in humans there are
limited data to support a mediating role for this cytokine. There may be
