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. 1995 Dec;86(4):636–645.

Impaired protein catabolism in Trypanosoma cruzi-infected macrophages: possible involvement in antigen presentation.

N Plasman 1, J G Guillet 1, B Vray 1
PMCID: PMC1384066  PMID: 8567032

Abstract

The effect of Trypanosoma cruzi infection on the ability of mature and immature murine peritoneal macrophage (MPM) subpopulations to catabolize the bacteriophage lambda repressor cI protein (cI) has been investigated. The capacity of infected MPM to present the cI and to stimulate various CD4+, I-Ad- or I-Ed-restricted T-cell hybridomas specific for cI was also assessed. Our results show that the radioiodinated cI uptake and catabolism decreased sharply after infection of MPM with T. cruzi. A cI presentation deficiency appeared in mature and immature MPM infected with T. cruzi trypomastigotes. The ability of infected MPM to bind immunogenic cI (12-26) peptides to the plasma membrane Ia molecules was also altered, especially in immature MPM, as shown with paraformaldehyde prefixed MPM, suggesting that these MPM only have a few functional Ia molecules on their membrane. The reduced capacity of cI presentation to the I-Ed-restricted B26.1 hybridomas by infected MPM subpopulations was comparable to that of the I-Ad-restricted B24.4 and B26.2 T cells. The percentage of major histocompatibility complex (MHC) class II-positive MPM was also reduced after T. cruzi infection. The percentage of positive interleukin-2 receptor (IL-2R) MPM was sharply lowered in infected cells, even with a pre- or a post-interferon-gamma (IFN-gamma) activation. Finally, inhibition of prostaglandin with indomethacin, or of nitric oxide with N-monomethyl-L-arginine, or of tumour necrosis factor-alpha (TNF-alpha) with specific monoclonal antibodies did not restore the cI presentation capacities of the MPM subpopulations. Taken together, these results suggest that T. cruzi infection induces a reduced capacity for macrophages to take up and catabolize antigen, resulting in a deficient antigen processing and presentation of the derived immunogenic peptides to specific CD4+ T-helper type-1 cell hybridomas. The decreased cI presenting capacity was a function of the cell's burden and maturity.

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Selected References

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