The apicomplexan pathogen Neospora caninum inhibits host cell apoptosis in the absence of discernible NF-kappa B activation.
Neospora caninum, a causative agent of bovine abortions, is an apicomplexan parasite that is closely related to the human pathogen Toxoplasma gondii. Since a number of intracellular parasites, including T. gondii, have been shown to modulate host cell apoptosis, the present study was conducted to establish whether N. caninum is similarly capable of subverting apoptotic pathways in its host cells. Our results indicated that death receptor-mediated apoptosis is repressed during N. caninum infection, and the data further showed that the executioner caspase, caspase 3, does not become activated in the infected cells. Surprisingly, nuclear translocation of the NF-kappaB subunit p65 was not detected in N. caninum-infected cells, although this host transcription factor has been shown to upregulate prosurvival genes in cells infected with T. gondii. Consistent with these findings, the distinct accumulation of phosphorylated IkappaB that is seen at the parasitophorous vacuole membrane (PVM) of T. gondii was not apparent on the N. caninum PVM. Although a putative IkappaB kinase activity was detected in N. caninum extracts, thereby implying that this parasite is capable of modulating NF-kappaB translocation into the host cell nucleus, the data collectively suggest that a profound and sustained activation of the NF-kappaB pathway is not central to the ability of N. caninum to prevent apoptosis of their host cells.
Herman
Rebecca K
RK
Department of Veterinary Science, 108 Gluck Equine Research Center, University of Kentucky, Lexington, KY 40546-0099, USA.
Molestina
Robert E
RE
Sinai
Anthony P
AP
Howe
Daniel K
DK
D021581:Active Transport, Cell Nucleus; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D002417:Cattle; D002460:Cell Line; D004247:DNA / Q000037:antagonists & inhibitors / Q000378:metabolism; D004249:DNA Damage; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism / Q000469:parasitology; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D018688:Neospora / Q000502:physiology*; D053218:Receptors, Death Domain / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism
D061945:Caspase Inhibitors; D016328:NF-kappa B; D053218:Receptors, Death Domain; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D004247:DNA; D053148:Caspase 3