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Infection and Immunity, November 2002, p. 6180-6187, Vol. 70, No. 11
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.11.6180-6187.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Infection Stage-Dependent Modulation of Macrophage Activation in Trypanosoma congolense-Resistant and -Susceptible Mice

Wim Noël,1 Gholamreza Hassanzadeh,1 Geert Raes,1 Boniface Namangala,2 Inge Daems,1 Lea Brys,1 Frank Brombacher,3 Patrick De Baetselier,1 and Alain Beschin1*

Department of Immunology, Parasitology and Ultrastructure, Flemish Interuniversity Institute for Biotechnology, Free University Brussels, B-1640 St-Genesius-Rode, Belgium,1 Department of Paraclinical Studies, University of Zambia School of Veterinary Medicine, Lusaka, Zambia,2 Department of Immunology, University of Cape Town, Groote Schuur Hospital, 7925 Cape Town, South Africa3

Received 28 December 2001/ Returned for modification 26 March 2002/ Accepted 17 August 2002

The contribution of cytokines and chemokines to resistance and susceptibility to African trypanosomiasis remains controversial. In the present study, the levels of type I and type II cytokines and of the MCP-1 chemokine were compared during the early and late stages of Trypanosoma congolense infection in susceptible BALB/c and resistant C57BL/6 mice. Moreover, the status of macrophage activation was compared in these animals by analyzing the inducible nitric oxide synthase-arginase balance, tumor necrosis factor secretion, and expression of the FIZZ1 and YM genes. Data show that changing from a predominant type I cytokine environment in the early stage of infection to a predominant type II cytokine environment and an enhanced MCP-1 secretion in the late stage of infection correlates with resistance to T. congolense. Concomitantly, macrophage activation evolves from a classical to a predominant alternative phenotype. We further confirmed that the simultaneous occurrence of type I/type II cytokines in the early stage of infection in susceptible BALB/c mice, reflected by the presence of macrophages exhibiting a mixed classical/alternative activation phenotype, is associated with uncontrolled parasite growth and early death. Interleukin-4 (IL-4) and IL-13 signaling did not influence the susceptibility of BALB/c mice to T. congolense infection and interestingly were not the main trigger to alternative macrophage activation. In T. congolense-resistant C57BL/6 mice, our results corroborated the induction of FIZZ1 and YM gene expressions with the alternative pathway of macrophage activation. In susceptible BALB/c mice, however, YM but not FIZZ1 induction reflected the emergence of alternatively activated macrophages. Hence, the FIZZ1 and YM genes may be useful markers to discriminate between distinct populations of alternatively activated macrophages.

* Corresponding author. Mailing address: Cellular Immunology Unit, Flemish Interuniversity Institute for Biotechnology, VIB-VUB, Paardenstraat 65, B-1640 St-Genesius-Rode, Belgium. Phone: 0032/2.359.0302. Fax: 0032/2.359.0359. E-mail: abeschin{at}vub.ac.be.

Editor: J. M. Mansfield

Infection and Immunity, November 2002, p. 6180-6187, Vol. 70, No. 11
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.11.6180-6187.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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