SRC-3 deficiency protects host from Listeria monocytogenes infection through increasing ROS production and decreasing lymphocyte apoptosis.

Abstract Listeria monocytogenes is the third major cause of death among food poisoning. Our previous studies have demonstrated that steroid receptor coactivator 3 (SRC-3) plays a critical protective role in host defense against extracellular bacterial pathogens such as Escherichia coli and Citrobacter rodentium. However, its role involved in intracellular bacterial pathogen infection remains unclear. Herein, we found that SRC-3−/− mice are more resistant to L. monocytogenes infection after tail intravenous injection with L. monocytogenes compared with wild-type mice. After infecting with L. monocytogenes, SRC-3−/− mice exhibited decreased mortality rate, decreased bacterial load, less body weight loss, less proinflammatory cytokines and less severe tissue damage compared with wild-type mice. SRC-3−/− mice produced more ROS and decreased L. monocytogenes-induced lymphocyte apoptosis. Mechanically, SRC-3−/− mice displayed decreased expressions of negative regulator of ROS (NRROS) and interferon (IFN)-β and its target genes such as Daxx, Mx1 and TRAIL associated with apoptosis. Taken together, SRC-3 deficiency can protect host from L. monocytogenes infection through increasing ROS production and decreasing lymphocyte apoptosis via affecting the expressions of NRROS and IFN-β.