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-Galactosylceramide Before Trypanosoma cruzi Infection Provides Protection or Induces Failure to Thrive1
Infectious Disease Research Institute, Seattle, WA 98104
Trypanosoma cruzi, a protozoan parasite, chronically
infects many mammalian species and triggers a chronic inflammatory
disease. Invariant V
14 NK T (iNKT) cells are a regulatory subset of
T cells that can contribute to protection against pathogens and to
control of chronic inflammatory diseases. -Galactosylceramide
(-GalCer) is an iNKT cell-specific glycolipid Ag: a single
immunization with -GalCer stimulates robust IFN-
and IL-4
production by iNKT cells, while multiple immunizations stimulate IL-4
production, but limited IFN- production. We recently demonstrated
that iNKT cells help control T. cruzi infection and
affect the chronic Ab response. Therefore, -GalCer treatment might
be used to increase protection or decrease chronic inflammation during
T. cruzi infection. In this report, we show that a
single dose of -GalCer before T. cruzi infection
decreases parasitemia. This protection is independent of IL-12, but
dependent upon iNKT cell IFN-. In addition, -GalCer treatment of
the IFN--/- mice exacerbates parasitemia through IL-4
production. Furthermore, a multiple dose regimen of -GalCer before
T. cruzi infection does not lower parasitemia and,
surprisingly, after parasitemia has resolved, causes poor weight gain.
These data demonstrate that during T. cruzi infection
glycolipids can be used to manipulate iNKT cell responses and suggest
the possibility of developing glycolipid treatments that can increase
protection and possibly decrease the chronic inflammatory
pathology.
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