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Vol. 11, Issue 1, 153-160, January 2000

Cell-specific Activation of Nuclear Factor-B by the Parasite Trypanosoma cruzi Promotes Resistance to Intracellular Infection

Belinda S. Hall,^* Winnie Tam, Ranjan Sen, and Miercio E. A. Pereira^*

 ^*Parasitology Research Center, Department of Pathology, Tufts University Medical School, Boston, Massachusetts 02111; and  Department of Molecular and Cellular Biology, Rosentiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454

The transcription factor nuclear factor-B (NF-B) is central to the innate and acquired immune response to microbial pathogens, coordinating cellular responses to the presence of infection. Here we demonstrate a direct role for NF-B activation in controlling intracellular infection in nonimmune cells. Trypanosoma cruzi is an intracellular parasite of mammalian cells with a marked preference for infection of myocytes. The molecular basis for this tissue tropism is unknown. Trypomastigotes, the infectious stage of T. cruzi, activate nuclear translocation and DNA binding of NF-B p65 subunit and NF-B-dependent gene expression in epithelial cells, endothelial cells, and fibroblasts. Inactivation of epithelial cell NF-B signaling by inducible expression of the inhibitory mutant IBaM significantly enhances parasite invasion. T. cruzi do not activate NF-B in cells derived from skeletal, smooth, or cardiac muscle, despite the ability of these cells to respond to tumor necrosis factor- with NF-B activation. The in vitro infection level in these muscle-derived cells is more than double that seen in the other cell types tested. Therefore, the ability of T. cruzi to activate NF-B correlates inversely with susceptibility to infection, suggesting that NF-B activation is a determinant of the intracellular survival and tissue tropism of T. cruzi.

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Corresponding author. E-mail address: Mpereira{at}infonet.tufts.edu.

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Molecular Biology of the Cell
Vol. 11, 153-160, January 2000
Copyright © 2000 by The American Society for Cell Biology

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