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B1
*
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853; and
Eukaryotic Transcriptional Regulation Section, Regulation of Cell Growth Laboratory, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702
Control of microbial infection requires regulated induction of
NF-
B-dependent proinflammatory cytokines such as IL-12 and TNF-
.
Activation of this important transcription factor is driven by
phosphorylation-dependent degradation of the inhibitory IB molecule,
an event which enables NF-B translocation from the cytoplasm to the
nucleus. In this study, we show that intracellular infection of
macrophages with the protozoan parasite Toxoplasma
gondii induces rapid IB phosphorylation and degradation.
Nevertheless, NF-B failed to translocate to the nucleus, enabling
the parasite to invade cells without triggering proinflammatory
cytokine induction. Infected cells subsequently subjected to LPS
triggering were severely crippled in IL-12 and TNF- production, a
result of tachyzoite-induced blockade of NF-B nuclear translocation.
Our results are the first to demonstrate the ability of an
intracellular protozoan to actively interfere with the NF-B
activation pathway in macrophages, an activity that may enable parasite
survival within the host.
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