IMPAIRMENT OF MONOCYTIC FUNCTION DURING TRYPANOSOMA-CRUZI INFECTION

During acute infection, Trypanosoma cruzi, the etiologic agent of Chag as' disease, causes immunosuppression by mechanisms that are not fully delineated. Since mononuclear phagocytes are major target cells in tr ypanosomiasis, we investigated monocytic function during acute T. cruz i infection. A series of human monocyte and macrophage hybridomas, whi ch represent clonal expansions of subpopulations of human macrophages and possess many normal monocytic functions, were successfully infecte d with T. cruzi. Clones 63 and 53, chosen for stability in long-term c ulture, were studied extensively after infection with T. cruzi. Follow ing infection of clone 63, the trypomastigote did not transform into t he amastigote multiplicative form, suggesting that clone 63 did not su pport the entire T. cruzi life cycle. The typical life cycle was compl eted in clone 53, and thus, clone 53 was used in subsequent studies. F ollowing infection, clone 53 lost expression of class II antigens comp ared with uninfected cells (DR of 2.2% versus 29.3% and mean channel f luorescence intensity [mean channel] of 4.1 versus 30.5, DQ of 2.3% ve rsus 15.6% and mean channel of 5.4 versus 11.4, and DP of 6.3% versus 27.2% and mean channel of 10.3 versus 33.4). The expression of Class I antigens (87.9% versus 82.8%; mean channel, 20 versus 120) and the ad hesion molecules LFA-1 (72.9% versus 28.7%; mean channel, 50.7 versus 23.7) and LFA-3 (10.8% versus 0.7%; mean channel, 20.7 versus 15.1) wa s increased in infected cells compared with that in uninfected cells. Production of interleukin-1 alpha was decreased and interleukin-6 prod uction was increased in infected clone 53 compared with those in the u ninfected cells, while production of tumor necrosis factor alpha was i ncreased. Finally, infected clone 53 showed a decreased ability to pre sent antigen to major histocompatibility complex-matched T cells, whic h may relate to the absence of Class II antigens or to aberrant cytoki ne production. These data suggest that (i) only selected subpopulation s of human macrophages support T. cruzi replication and (ii) at least in some subpopulations, macrophage dysfunction may contribute to the a ltered immune function observed in Chagas' disease.