Analysis of macrophage activation in African trypanosomiasis.
African trypanosomes cause a fatal disease of man and animals that is characterized by extensive functional, histological, and pathological changes in the lymphoid tissues of infected hosts, including an increase in the numbers and activation state of macrophages. Macrophage activation during infection is the result of exposure of these cells to parasite components and host-derived IFN-gamma, produced in response to parasite antigens. The balance of these different activation signals may determine the outcome of infection. In the experiments described here, we assessed the ability of the variant surface glycoprotein (VSG) of the organism Trypanosoma brucei rhodesiense (T.b. rhodesiense) to activate macrophages directly. Our results demonstrate that macrophages bind and are activated by the VSG molecule. The resulting profile of activation differs from that stimulated by IFN-gamma. These results suggest that the interaction of host macrophages with VSG released during parasite infection may be a key component of trypanosomiasis.
Paulnock
D M
DM
Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison, Wisconsin 53706-1532, USA. paulnock@facstaff.wisc.edu
Coller
S P
SP
D000818:Animals; D002460:Cell Line; D005260:Female; D017261:Glycosylphosphatidylinositols / Q000097:blood / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008262:Macrophage Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D016833:Trypanosoma brucei rhodesiense / Q000276:immunology*; D014353:Trypanosomiasis, African / Q000097:blood / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000097:blood / Q000276:immunology*
D017261:Glycosylphosphatidylinositols; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D014643:Variant Surface Glycoproteins, Trypanosoma; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse