| Abstract |
Cryptosporidium parvum (Cp) is an enteric,
intracellular parasite that causes significant morbidity,
particularly among people suffering from AIDS. There is no
effective treatment for AIDS-related cryptosporidiosis. It
is well established that adaptive cell-mediated immunity is
necessary for immunity to Cp. However, even in the absence
of adaptive immunity, there appears to be an interferon ???IFN?)-dependent
resistance to Cp infection. The mechanism of this immune response
as well as the source of this cytokine is unknown. Using a
murine model of cryptosporidiosis, we have demonstrated an
IFN?-dependent resistance to the parasite 24 hours after infection.
We have also shown that intestinal intraepithelial lymphocytes
(iIELs) produce IFN? 24 hours after infection with Cp. The
iIELs are likely candidates for mediating rapid mucosal immune
responses to enteric pathogens by virtue of their location
and unique phenotype. The role of iIELs in resistance to Cp
infection in humans is not known. In this pilot project, we
will develop an in-vitro co-culture model using human iIELs
and intestinal epithelial cells in which the function of iIELs
can be directly studied. Using samples of human small intestine,
we will determine the effect of ex-vivo iIELs on Cp-infected
intestinal epithelial cells. We will also determine the phenotype
of the iIELs which respond to the Cp-infected epithelial cell.
In addition, we will also study the mechanism by which iIELs
affect Cp infection in these cells. This model will add to
our understanding of human mucosal immune responses to enteric
pathogens in conditions characterized by the lack of adaptive
immune system.
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