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Infection and Immunity, September 2004, p. 5283-5291, Vol. 72, No. 9
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.9.5283-5291.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Monocytes from Patients with Indeterminate and Cardiac Forms of Chagas' Disease Display Distinct Phenotypic and Functional Characteristics Associated with Morbidity

Paulo E. A. Souza,1,2 Manoel O. C. Rocha,3 Etel Rocha-Vieira,4 Cristiane A. S. Menezes,1 Andréa C. L. Chaves,5 Kenneth J. Gollob,4 and Walderez O. Dutra1*

Department of Morphology, Institute of Biological Sciences,1 Graduate Course in Pathology,2 Tropical Medicine Graduate Course, Medical Center,3 Department of Biochemistry-Immunology, Institute of Biological Sciences, Universidade Federal da Minas Gerais,4 Centro de Pesquisas René-Rachou FIOCRUZ and Pontificia Universidade Católica de Minas Gerais, Belo Horizonte, Brazil5

Received 9 February 2004/ Returned for modification 15 April 2004/ Accepted 9 May 2004

Many studies have demonstrated that monocyte-derived macrophages display critical activities in immunity to parasites. The ability of these cells to process and present antigens, produce cytokines, and provide costimulatory signals demonstrates their pivotal role in initiating immune responses. Although potential modulatory function has been attributed to monocytes from patients with Chagas' disease, a systematic phenotypic and functional analysis of these cells has not been performed. In this work, we analyzed the ex vivo expression of important surface molecules (CD11b and HLA-DR) and immunoregulatory cytokines (interleukin-10 [IL-10], IL-12 and tumor necrosis factor alpha [TNF-{alpha}]) in CD14+ and CD14 monocytes from Chagas' disease patients with polar clinical forms of the disease: indeterminate or severe cardiac. We also evaluated the influence of in vitro infection with T. cruzi in the expression of such molecules. We observed that monocytes from indeterminate-disease patients display lower levels of HLA-DR than those from noninfected individuals both ex vivo and after in vitro infection with T. cruzi. Although ex vivo expression of CD11b was similar among the groups, in vitro infection led to decreased expression of this molecule by monocytes from Chagas' disease patients but not from noninfected individuals. Analysis of the expression of immunoregulatory cytokines showed that while monocytes from indeterminate-disease patients are committed to IL-10 expression, a higher percentage of monocytes from cardiac-disease patients express TNF-{alpha} after exposure to live parasites. These results suggest that monocytes from indeterminate-disease patients display modulatory characteristics related to low HLA-DR and high IL-10 expression whereas monocytes from cardiac-disease, patients may be committed to induction of inflammatory responses related to high TNF-{alpha} expression.


* Corresponding author. Mailing address: Laboratório de Biologia das Interações Celulares, Bloco N3, Sala 302, Departamento de Morfologia do Instituto de Ciências Biológicas da Universidade Federal de Minas Gerais, Avid. Antônio Carlos, 6627, Pampulha, CEP 31270-901, Belo Horizonte-MG, Brazil. Phone: 55 (31) 34992809. Fax: 55 (31) 34992655. E-mail: waldutra{at}mono.icb.ufmg.br.

Editor: W. A. Petri, Jr.


Infection and Immunity, September 2004, p. 5283-5291, Vol. 72, No. 9
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.9.5283-5291.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Souza, P. E. A., Rocha, M. O. C., Menezes, C. A. S., Coelho, J. S., Chaves, A. C. L., Gollob, K. J., Dutra, W. O. (2007). Trypanosoma cruzi Infection Induces Differential Modulation of Costimulatory Molecules and Cytokines by Monocytes and T Cells from Patients with Indeterminate and Cardiac Chagas' Disease. Infect. Immun. 75: 1886-1894 [Abstract] [Full Text]  
  • Chang, H. K., Thalhofer, C., Duerkop, B. A., Mehling, J. S., Verma, S., Gollob, K. J., Almeida, R., Wilson, M. E. (2007). Oxidant Generation by Single Infected Monocytes after Short-Term Fluorescence Labeling of a Protozoan Parasite. Infect. Immun. 75: 1017-1024 [Abstract] [Full Text]