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Denise M. Monack^*, Joan Mecsas^*, Donna Bouley, and Stanley Falkow^*

From the ^* Department of Microbiology and Immunology and the Department of Comparative Medicine, Stanford School of Medicine, Stanford University, Stanford, California 94305

Pathogenic Yersinia cause a systemic infection in mice that is dependent on the presence of a large plasmid encoding a number of secreted virulence proteins called Yops. We previously demonstrated that a plasmid-encoded Yop, YopJ, was essential for inducing apoptosis in cultured macrophages. Here we report that YopJ is a virulence factor in mice and is important for the establishment of a systemic infection. The oral LD₅₀ for a yopJ mutant Yersinia pseudotuberculosis increases 64-fold compared with wild-type. Although the yopJ mutant strain is able to reach the spleen of infected mice, the mutant strain seldom reaches the same high bacterial load that is seen with wild-type Yersinia strain and begins to be cleared from infected spleens on day 4 after infection. Furthermore, when in competition with wild-type Yersinia in a mixed infection, the yopJ mutant strain is deficient for spread from the Peyer's patches to other lymphoid tissue. We also show that wild-type Yersinia induces apoptosis in vivo of Mac-1⁺ cells from infected mesenteric lymph nodes or spleens, as measured by quantitative flow cytometry of TUNEL (Tdt-mediated dUTP–biotin nick-end labeling)-positive cells. The levels of Mac-1⁺, TUNEL⁺ cells from tissue infected with the yopJ mutant strain were equivalent to the levels detected in cells from uninfected tissue. YopJ is necessary for the suppression of TNF- production seen in macrophages infected with wild-type Yersinia, based on previous in vitro studies (Palmer, L.E., S. Hobbie, J.E. Galan, and J.B. Bliska. 1998. Mol. Microbiol. 27:953–965). We conclude here that YopJ plays a role in the establishment of a systemic infection by inducing apoptosis and that this is consistent with the ability to suppress the production of the proinflammatory cytokine tumor necrosis factor .

Key Words: YopJ • virulence • macrophages • TUNEL reactions • Mac-1 antibody

Abbreviations used: MLNs, mesenteric lymph nodes; PP, Peyer's patches; TUNEL, Tdt-mediated dUTP–biotin nick-end labeling.

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This article has been cited by other articles:

• Bergsbaken, T., Cookson, B. T. (2009). Innate immune response during Yersinia infection: critical modulation of cell death mechanisms through phagocyte activation. J. Leukoc. Biol. 86: 1153-1158 [Abstract] [Full Text]  

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