Modulation of NF-kappaB activation in Theileria annulata-infected cloned cell lines is associated with detection of parasite-dependent IKK signalosomes and disruption of the actin cytoskeleton.
Apicomplexan parasites within the genus Theileria have the ability to induce continuous proliferation and prevent apoptosis of the infected bovine leukocyte. Protection against apoptosis involves constitutive activation of the bovine transcription factor NF-kappaB in a parasite-dependent manner. Activation of NF-kappaB is thought to involve recruitment of IKK signalosomes at the surface of the macroschizont stage of the parasite, and it has been postulated that additional host proteins with adaptor or scaffolding function may be involved in signalosome formation. In this study two clonal cell lines were identified that show marked differences in the level of activated NF-kappaB. Further characterization of these lines demonstrated that elevated levels of activated NF-kappaB correlated with increased resistance to cell death and detection of parasite-associated IKK signalosomes, supporting results of our previous studies. Evidence was also provided for the existence of host- and parasite-dependent NF-kappaB activation pathways that are influenced by the architecture of the actin cytoskeleton. Despite this influence, it appears that the primary event required for formation of the parasite-dependent IKK signalosome is likely to be an interaction between a signalosome component and a parasite-encoded surface ligand.
Division of Molecular Pathobiology, Department of Clinical Research and VPH, Vetsuisse Faculty Bern, Bern, Switzerland.
Jacqueline
J
Schmuckli-Maurer
Jane
J
Kinnaird
Sreerekha
S
Pillai
Pascal
P
Hermann
Sue
S
McKellar
William
W
Weir
Dirk
D
Dobbelaere
Brian
B
Shiels
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006790:Host-Parasite Interactions; D051550:I-kappa B Kinase / Q000378:metabolism*; D015151:Immunoblotting; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D016796:Theileria annulata / Q000378:metabolism* / Q000502:physiology
D000199:Actins; D016328:NF-kappa B; D051550:I-kappa B Kinase