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Infection and Immunity, September 2007, p. 4255-4262, Vol. 75, No. 9
0019-9567/07/$08.00+0     doi:10.1128/IAI.00418-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Apicomplexan Pathogen Neospora caninum Inhibits Host Cell Apoptosis in the Absence of Discernible NF-B Activation

Department of Veterinary Science,¹ Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, Kentucky 40546²

Received 21 March 2007/ Returned for modification 26 April 2007/ Accepted 7 June 2007

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-B 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 IB that is seen at the parasitophorous vacuole membrane (PVM) of T. gondii was not apparent on the N. caninum PVM. Although a putative IB kinase activity was detected in N. caninum extracts, thereby implying that this parasite is capable of modulating NF-B translocation into the host cell nucleus, the data collectively suggest that a profound and sustained activation of the NF-B pathway is not central to the ability of N. caninum to prevent apoptosis of their host cells.

Published ahead of print on 18 June 2007.

Editor: J. F. Urban, Jr.