The intracellular parasite Theileria parva protects infected T cells from apoptosis.
Parasites have evolved a plethora of strategies to ensure their survival. The intracellular parasite Theileria parva secures its propagation and spreads through the infected animal by infecting and transforming T cells, inducing their continuous proliferation and rendering them metastatic. In previous work, we have shown that the parasite induces constitutive activation of the transcription factor NF-kappaB, by inducing the constitutive degradation of its cytoplasmic inhibitors. The biological significance of NF-kappaB activation in T. parva-infected cells, however, has not yet been defined. Cells that have been transformed by viruses or oncogenes can persist only if they manage to avoid destruction by the apoptotic mechanisms that are activated on transformation and that contribute to maintain cellular homeostasis. We now demonstrate that parasite-induced NF-kappaB activation plays a crucial role in the survival of T. parva-transformed T cells by conveying protection against an apoptotic signal that accompanies parasite-mediated transformation. Consequently, inhibition of NF-kappaB nuclear translocation and the expression of dominant negative mutant forms of components of the NF-kappaB activation pathway, such as IkappaBalpha or p65, prompt rapid apoptosis of T. parva-transformed T cells. Our findings offer important insights into parasite survival strategies and demonstrate that parasite-induced constitutive NF-kappaB activation is an essential step in maintaining the transformed phenotype of the infected cells.
Heussler
V T
VT
Laboratory of Immunopathology, Institute of Animal Pathology, University of Berne, CH-3012 Berne, Switzerland.
Machado
J
J
Fernandez
P C
PC
Botteron
C
C
Chen
C G
CG
Pearse
M J
MJ
Dobbelaere
D A
DA
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002135:Calcium-Binding Proteins; D002417:Cattle; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000276:immunology; D006801:Humans; D020672:I-kappa B Proteins; D008562:Membrane Glycoproteins / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000276:immunology; D050863:Synaptotagmin I; D050857:Synaptotagmins; D013601:T-Lymphocytes / Q000276:immunology / Q000469:parasitology* / Q000473:pathology*; D016797:Theileria parva / Q000469:parasitology*; D013801:Theileriasis / Q000276:immunology* / Q000473:pathology
D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D050863:Synaptotagmin I; D050857:Synaptotagmins