Mycobacterium tuberculosis Eis Regulates Autophagy, Inflammation, and Cell Death through Redox-dependent Signaling

The “enhanced intracellular survival” (eis) gene of Mycobacterium tuberculosis (Mtb) is involved in the intracellular survival of M. smegmatis. However, its exact effects on host cell function remain elusive. We herein report that Mtb Eis plays essential roles in modulating macrophage autophagy, inflammatory responses, and cell death via a reactive oxygen species (ROS)-dependent pathway. Macrophages infected with an Mtb eis-deletion mutant H37Rv (Mtb-Δeis) displayed markedly increased accumulation of massive autophagic vacuoles and formation of autophagosomes in vitro and in vivo. Infection of macrophages with Mtb-Δeis increased the production of tumor necrosis factor-α and interleukin-6 over the levels produced by infection with wild-type or complemented strains. Elevated ROS generation in macrophages infected with Mtb-Δeis (for which NADPH oxidase and mitochondria were largely responsible) rendered the cells highly sensitive to autophagy activation and cytokine production. Despite considerable activation of autophagy and proinflammatory responses, macrophages infected with Mtb-Δeis underwent caspase-independent cell death. This cell death was significantly inhibited by blockade of autophagy and c-Jun N-terminal kinase-ROS signaling, suggesting that excessive autophagy and oxidative stress are detrimental to cell survival. Finally, artificial over-expression of Eis or pretreatment with recombinant Eis abrogated production of both ROS and proinflammatory cytokines, which depends on the N-acetyltransferase domain of the Eis protein. Collectively, these data indicate that Mtb Eis suppresses host innate immune defenses by modulating autophagy, inflammation, and cell death in a redox-dependent manner

Upper-secondary educational trajectories and young men’s and women’s self-esteem development in Switzerland

Adolescents’ self-esteem is an important indicator of their successful development and their well-being. This paper investigates the impact of educational trajectories on the development of women’s and men’s self-esteem from mid to late adolescence in Switzerland. We posit that cooling-out processes after educational failure, leading to a decrease in self-esteem, are more frequent among women than men attributable to particular institutional characteristics of the stratified educational system in Switzerland and gender differences in the salience of social comparison. Analyses are based on the middle cohort of the Swiss Survey of Children and Youth (COCON). The first three survey waves (2006–2009) were conducted when the respondents were 15, 16 and 18 years old. Self-esteem development was examined by using latent growth-curve models. Analyses show a boost of self-esteem both at the mean-level and the intra-individual level for all adolescents. However, the impact of educational success or failure in the years following the transition to post-compulsory education differs by gender. The evidence suggests that women’s self-esteem development is more affected by educational attainment than men’s