Infection stage-dependent modulation of macrophage activation in Trypanosoma congolense-resistant and -susceptible mice

Autor: Geert Raes, Boniface Namangala, Gholamreza Hassanzadeh, Patrick De Baetselier, Alain Beschin, Inge Daems, Frank Brombacher, Wim Noël, Lea Brys
Přispěvatelé: Cellular and Molecular Immunology, Chemical Engineering and Industrial Chemistry, Vrije Universiteit Brussel
Rok vydání: 2002
Předmět:
Zdroj: Vrije Universiteit Brussel
ISSN: 0019-9567
Popis: 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 ofTrypanosoma congolenseinfection 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 toT. 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 toT. congolenseinfection and interestingly were not the main trigger to alternative macrophage activation. InT. 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.
Databáze: OpenAIRE