A stage-specific, parasite-induced, "window" of in vivo interferon-gamma production is associated with pathogenesis in Theileria annulata infection.
The tick-borne protozoan parasite Theileria annulata causes tropical theileriosis, a severe leukoproliferative disease of cattle, which naive susceptible animals fail to control. The parasite infects and transforms macrophages, developing in the local draining lymph node. IFN gamma has been shown to block parasite development in newly infected cells, and inhibits the growth of fully differentiated macroschizont stage-infected cells in vitro. However, the parasite has been found to specifically induce IFN gamma production by T cells and appears to flourish in the face of this T cell-derived response in vivo. Here we show that the production of IFN gamma in vivo is tightly controlled by the parasite. Induction of cytokine production by T cells is not initiated until the parasite has developed beyond the IFN gamma sensitive trophozoite stage. Cytokine production is kept high as infected macrophages develop, and IFN gamma appears to play an active role in maintaining the growth of these cells. Once the infection is fully established, IFN gamma is down regulated, avoiding potential inhibitory effects. Thus by controlling T cell IFN gamma production, the parasite induces a "window" of cytokine expression which promotes its own growth, but avoids potential inhibitory effects of the cytokine.
CTVM, University of Edinburgh, Scotland, UK. jdmc1V@ccinmed.gla.ac.uk
J D
JD
Campbell
A K
AK
Nichani
D J
DJ
Brown
E J
EJ
Glass
R L
RL
Spooner
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000096:biosynthesis*; D008198:Lymph Nodes / Q000276:immunology / Q000469:parasitology; D008264:Macrophages / Q000276:immunology / Q000469:parasitology; D013601:T-Lymphocytes / Q000276:immunology; D016796:Theileria annulata / Q000254:growth & development / Q000276:immunology; D013801:Theileriasis / Q000276:immunology*; D013987:Ticks / Q000276:immunology
D007371:Interferon-gamma