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http://www.jimmunol.org/cgi/content/full/169/9/5202

Studies in animal models of intracellular bacterial infections

support our hypothesis that the importance of perforin-mediated

cytolysis in protective immunity is related to the ability of

bacteria to directly spread from cell to cell. Rickettsia sp. are

intracytoplasmic bacteria capable of direct cell-cell spread. In

agreement with a prediction of our model, protective immunity

against Rickettsia depends on perforin-mediated CD8 T cell

cytotoxicity (29). Although CD8 T cells have been established to

participate in defense against the intracellular pathogens Chlamydia

pneumoniae and Mycobacterium tuberculosis, perforin has been shown

to play a minimal role in controlling infections with these bacteria

(30, 31). Unlike Lm and Rickettsia, which are intracytoplasmic

pathogens, these bacteria reside within vacuolar compartments, which

may influence the contribution of perforin. However, perforin-

mediated cytolysis should release and expose both cytosolic and

vacuolar bacteria to macrophage and Ab-mediated immune mechanisms.

An alternative interpretation suggested by our model is that

perforin-independent control of Chlamydia and Mycobacterium relates

to their inability to spread directly from cell to cell without host

cell lysis.

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