IMPAIRED PROTEIN CATABOLISM IN TRYPANOSOMA CRUZI-INFECTED MACROPHAGES- POSSIBLE INVOLVEMENT IN ANTIGEN PRESENTATION

The effect of Trypanosoma cruzi infection on the ability of mature and immature murine peritoneal macrophage (MPM) subpopulations to catabol ize the bacteriophage lambda repressor cI protein (cI) has been invest igated. The capacity of infected MPM to present the cI and to stimulat e various CD4(+), I-A(d)- or I-E(d) restricted T-cell hybridomas speci fic for cI was also assessed. Our results show that the radioiodinated cI uptake and catabolism decreased sharply after infection of MPM wit h T. cruzi. A cI presentation deficiency appeared in mature and immatu re 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 show n 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-E(d)-restricted B26.1 hybridomas by infected MPM subpopulations was comparable to that of the I-A(d)-restricted B2 4.4 and B26.2 T cells. The percentage of major histocompatibility comp lex (MHC) class II-positive MPM was also reduced after T. cruzi infect ion. The percentage of positive interleukin-2 receptor (IL-2R) MPM was sharply lowered in infected cells, even with a pre- or a post-interfe ron-2 (IFN-gamma) activation. Finally, inhibition of prostaglandin wit h indomethacin. or of nitric oxide with N-monomethyl-L-arginine, or of tumour necrosis factor-alpha (TNF-alpha) with specific monoclonal ant ibodies did not restore the cI presentation capacities of the MPM subp opulations. Taken together, these results suggest that T. cruzi infect ion induces a reduced capacity for macrophages to take up and cataboli ze antigen, resulting in a deficient antigen processing and prese ntat ion of the derived immunogenic peptides to specific CD4(+) T-helper ty pe-1 cell hybridomas. The decreased cI presenting capacity was a funct ion of the cell's burden and maturity.