Constitutive PI3-K activity is essential for proliferation, but not survival, of Theileria parva-transformed B cells.
Theileria is an intracellular parasite that causes lymphoproliferative disorders in cattle, and infection of leucocytes induces a transformed phenotype similar to tumour cells, but the mechanisms by which the parasite induces this phenotype are not understood. Here, we show that infected B lymphocytes display constitutive phosphoinositide 3-kinase (PI3-K) activity, which appears to be necessary for proliferation, but not survival. Importantly, we demonstrate that one mechanism by which PI3-K mediates the proliferation of infected B lymphocytes is through the induction of a granulocyte-monocyte colony-stimulating factor (GM-CSF)-dependent autocrine loop. PI3-K induction of GM-CSF appears to be at the transcriptional level and, consistently, we demonstrate that PI3-K is also involved in the constitutive induction of AP-1 and NF-kappaB, which characterizes Theileria-infected leucocytes. Taken together, our results highlight a novel strategy exploited by the intracellular parasite Theileria to induce continued proliferation of its host leucocyte.
Baumgartner
M
M
Département d'Immunologie, Institut Pasteur, Paris, France.
Chaussepied
M
M
Moreau
M F
MF
Werling
D
D
Davis
W C
WC
Garcia
A
A
Langsley
G
G
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000469:parasitology*; D002417:Cattle; D002455:Cell Division; D002461:Cell Line, Transformed; D002470:Cell Survival; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000378:metabolism; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D016797:Theileria parva / Q000472:pathogenicity*; D018808:Transcription Factor AP-1 / Q000032:analysis / Q000378:metabolism; D015533:Transcriptional Activation
D016328:NF-kappa B; D018808:Transcription Factor AP-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019869:Phosphatidylinositol 3-Kinases