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Impairment of monocytic function during Trypanosoma cruzi infection
M J Louie1, W R Cuna, C Rodriguez De Cuna
1Division of Clinical Immunology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Insights
Trypanosoma cruzi infection of human monocytic cells alters immune responses. Infected cells showed reduced Class II antigen expression and altered cytokine production, contributing to immunosuppression in Chagas
Area of Science:
- Immunology
- Infectious Diseases
- Cell Biology
Background:
- Trypanosoma cruzi causes immunosuppression during acute infection through incompletely understood mechanisms.
- Mononuclear phagocytes are key targets in Chagas' disease, making their function critical to study.
Purpose of the Study:
- To investigate the functional changes in human monocytic cells upon infection with Trypanosoma cruzi.
- To identify alterations in antigen expression, adhesion molecule presence, and cytokine production.
Main Methods:
- Infection of human monocyte-macrophage hybridoma clone 53 with Trypanosoma cruzi.
- Flow cytometry analysis of Class I and Class II antigen expression.
- Assessment of adhesion molecules LFA-1 and LFA-3 expression.
- Quantification of interleukin-1 alpha, interleukin-6, and tumor necrosis factor alpha production.
Main Results:
- Infected clone 53 cells exhibited significantly decreased expression of Class II antigens (DR, DQ, DP).
- Expression of Class I antigens and adhesion molecules LFA-1 and LFA-3 increased in infected cells.
- Interleukin-1 alpha production decreased, while interleukin-6 and tumor necrosis factor alpha production increased in infected cells.
Conclusions:
- Trypanosoma cruzi infection profoundly alters human monocytic cell phenotype and function.
- These changes, including reduced Class II antigen expression and modified cytokine profiles, likely contribute to the immunosuppression observed in Chagas' disease.
Abstract:
During acute infection, Trypanosoma cruzi, the etiologic agent of Chagas' disease, causes immunosuppression by mechanisms that are not fully delineated. Since mononuclear phagocytes are major target cells in trypanosomiasis, we investigated monocytic function during acute T. cruzi infection. A series of human monocyte and macrophage hybridomas, which represent clonal expansions of subpopulations of human macrophages and possess many normal monocytic functions, were successfully infected with T. cruzi. Clones 63 and 53, chosen for stability in long-term culture, were studied extensively after infection with T. cruzi. Following infection of clone 63, the trypomastigote did not transform into the amastigote multiplicative form, suggesting that clone 63 did not support the entire T. cruzi life cycle. The typical life cycle was completed in clone 53, and thus, clone 53 was used in subsequent studies. Following infection, clone 53 lost expression of class II antigens compared with uninfected cells (DR of 2.2% versus 29.3% and mean channel fluorescence intensity [mean channel] of 4.1 versus 30.5, DQ of 2.3% versus 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 adhesion 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) was increased in infected cells compared with that in uninfected cells. Production of interleukin-1 alpha was decreased and interleukin-6 production was increased in infected clone 53 compared with those in the uninfected cells, while production of tumor necrosis factor alpha was increased.(ABSTRACT TRUNCATED AT 250 WORDS)