Listeria monocytogenes induces T cell receptor unresponsiveness via its pore-forming toxin listeriolysin O

The success of many pathogens relies on their ability to circumvent the innate and adaptive immune defenses. How bacterial pathogens subvert host responses is not clear. Cholesterol-dependent cytolysins (CDCs) represent an expansive family of homologous pore-forming toxins produced by more than 20 Gram-positive bacterial species. Here we show that listeriolysin O (LLO), a prototype CDC produced by Listeria monocytogenes, inhibits antigen receptor-induced T cell proliferation. In vivo proliferation of OT II T cells was highly diminished in the presence of wild type but not the LLO-deficient bacteria. T cells pre-exposed to LLO ex vivo were also impaired in proliferation upon TCR activation in vivo and in vitro. Our results suggest that LLO-induced T cell unresponsiveness is due to the sub-threshold activation of T cells via the induction of a calcium-NFAT dependent transcriptional program that drives the expression of negative regulators of TCR signaling.

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Gekara NO, Zietara N, Geffers R, Weiss S