Theileria parva: taking control of host cell proliferation and survival mechanisms.
The intracellular parasite Theileria parva infects and transforms bovine T-cells, inducing their uncontrolled proliferation and spread in non-lymphoid as well as lymphoid tissues. This parasite-induced transformation is the predominant factor contributing to the pathogenesis of a lymphoproliferative disease, called East Coast fever. T. parva-transformed cells become independent of antigenic stimulation or exogenous growth factors. A dissection of the signalling pathways that are activated in T. parva-infected cells shows that the parasite bypasses signalling pathways that normally emanate from the T-cell antigen receptor to induce continuous proliferation. This review concentrates on the influence of the parasite on the state of activation of the mitogen-activated protein kinase (MAPK), NF-kappaB and phosphoinositide-3-kinase (PI3-K) pathways in the host cell. Of the MAPKs, JNK, but not ERK or p38, is active, inducing constitutive activation of the transcription factors AP-1 and ATF-2. A crucial step in the transformation process is the persistent activation of the transcription factor NF-kappaB, which protects T. parva-transformed cells from spontaneous apoptosis accompanying the transformation process. Inhibitor studies also suggest an important role for the lipid kinase, PI-3K, in the continuous proliferation of T. parva-transformed lymphocytes.
Dobbelaere
D A
DA
Institute of Animal Pathology, Molecular Pathology, Berne, Switzerland. dirk.dobbelaere@itpa.unibe.ch
Fernandez
P C
PC
Heussler
V T
VT
D000818:Animals; D002417:Cattle; D006790:Host-Parasite Interactions; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000469:parasitology* / Q000502:physiology; D016797:Theileria parva / Q000472:pathogenicity* / Q000502:physiology*; D013801:Theileriasis / Q000469:parasitology