Serine/Threonine Protein Kinase Stk Is Required for Virulence, Stress Response, and Penicillin Tolerance in Streptococcus pyogenes▿

Genes encoding one or more Ser/Thr protein kinases have been identified recently in many bacteria, including one (stk) in the human pathogen Streptococcus pyogenes (group A streptococcus [GAS]). We report that in GAS, stk is required to produce disease in a murine myositis model of infection. Using microarray and quantitative reverse transcription-PCR (qRT-PCR) studies, we found that Stk activates genes for virulence factors, osmoregulation, metabolism of α-glucans, and fatty acid biosynthesis, as well as genes affecting cell wall synthesis. Confirming these transcription studies, we determined that the stk deletion mutant is more sensitive to osmotic stress and to penicillin than the wild type. We discuss several possible Stk phosphorylation targets that might explain Stk regulation of expression of specific operons and the possible role of Stk in resuscitation from quiescence

Mechanisms of naive CD4+ T cell maintenance in the elderly and its implications for Autoimmunity

CD4+ T cells are critical players in the immune system. CD4+ T cells coordinate both innate and adaptive immune responses. When naive CD4+ T cells become activated via their antigen-specific T cell receptor in the presence of costimulation, these cells differentiate into effector and memory T cells. Maintenance of a large and diverse naive CD4+ T cell repertoire over time is thus essential for developing immunity to a multitude of novel antigens. Despite a strong decline in thymic production of naive CD4+ T cells with aging, the circulating pool of naive CD4+ T cells is well-maintained in elderly humans. The preservation of naive CD4+ T cells in aged subjects contrasts sharply with that of naive CD8+ T cells, which decline markedly with age. In the current chapter, the mechanisms facilitating the remarkable maintenance of the naive CD4+ T cell pool with age are discussed. Important mechanisms include recognition of self-peptides by T cell receptors and stimulation by homeostatic cytokines, including interleukin-7 and interleukin-2. Furthermore, we address the implications of naive CD4+ T cell maintenance for the development of autoimmune diseases in the elderly. Lastly, two models for the development of aging-associated autoimmunity are proposed, and suggestions for further investigation are provided