Infection stage-dependent modulation of macrophage activation in Trypanosoma congolense-resistant and -susceptible mice.
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.
Noël
Wim
W
Department of Immunology, Parasitology and Ultrastructure, Flemish Interuniversity Institute for Biotechnology, Free University Brussels, B-1640 St-Genesius-Rode, Belgium.
Hassanzadeh
Gholamreza
G
Raes
Geert
G
Namangala
Boniface
B
Daems
Inge
I
Brys
Lea
L
Brombacher
Frank
F
Baetselier
Patrick De
PD
Beschin
Alain
A
D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004198:Disease Susceptibility; D036341:Intercellular Signaling Peptides and Proteins; D018793:Interleukin-13 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D008262:Macrophage Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor; D018512:Parasitemia / Q000276:immunology; D011506:Proteins / Q000235:genetics; D014348:Trypanosoma congolense; D014353:Trypanosomiasis, African / Q000276:immunology*
D018932:Chemokine CCL2; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D018793:Interleukin-13; D011506:Proteins; C413576:Retnla protein, mouse; D015847:Interleukin-4; D020932:Nerve Growth Factor