Mitogen-Activated Protein Kinase-Activated Protein Kinase 2-Deficien Mice Show Increased Susceptibility to Listeria monocytogenes Infection

Mitogen-activated protein kinase-activated protein kinase 2 (MK2) is one of several kinases activated through direct phosphorylation by p38 mitogen-activated protein kinase. MK2 regulates LPS-induced TNF mRNA translation, and targeted mutation of the MK2 gene renders mice more resistant to D-galactosamine plus LPS-induced liver damage. In the present study, we investigated the role of MK2 in immune defense against Listeria monocytogenes infection. MK2-deficien mice displayed diminished resistance to L. monocytogenes due to impaired control of bacterial growth. The increase in bacterial load in MK2 / mice was associated with normal levels of IL-1 , IL-6, and IFN, whereas TNF production was strongly attenuated. In line, MK2-deficien bone marrow-derived macrophages showed impaired release of TNF, but not of IL-1 , in response to various bacterial stimuli in addition to decreased phagocytosis of fluorescence-labele bacteria. Furthermore, spleen cells from MK2 / mice displayed diminished IFNsynthesis after stimulation with L. monocytogenes. In contrast, MK2 deficienc had no effect on macrophage generation of NO or on oxidative burst activity in response to L. moocytogenes. These results indicate an essential role of MK2 in host defense against intracellular bacteria probably via regulation of TNF and IFNproduction required for activation of antibacterial effector mechanisms.