All That Glisters Is Not Gold - <b><i>Staphylococcus aureus</i></b> and Innate Immunity

light of this, novel understanding of innate immune mechanisms can provide templates for novel antimicrobial pharmaceuticals. Recently, several virulence strategies of S. aureus have been elucidated. The S. aureus α-toxin is a pore-forming toxin that utilizes the receptor ADAM10 to injure cells of the host. Utilizing myeloid lineage-specific Adam10 knockout mice, Becker et al. [5] have shown that α-toxin causes tissue-specific effects on innate immunity. The effects correlated with a defect in toxin-induced IL-1β production. The S. aureus α-toxin also plays other roles in corrupting innate immunity. After phagocytosis by macrophages, S. aureus evades killing in an α-toxin-dependent manner, and then prevents the apoptosis of infected cells by upregulating expression of antiapoptotic genes. Using purified α-toxin, Koziel et al. [6] have shown that α-toxin is critical for the induction of MCL-1 expression and the cytoprotection of infected macrophages. Recognition and signaling through Toll-like receptors are crucial molecules in the induction of host defense responses. This requires adaptor proteins that contain a Toll/ interleukin-1 receptor (TIR) domain. S. aureus produces several innate immune-evasion molecules that interfere with the host’s innate immune response. Askarian et al. [7] found a homologue of the human TIR domain in S. aureus In this issue of Journal of Innate Immunity , Dai et al. [1] discuss myeloid-derived suppressor cells (MDSCs) in an interesting review. MDSCs are a heterogeneous population of immature suppressor cells that are generated due to aberrant myelopoiesis under pathological conditions. These cells have immunosuppressive properties and may contribute to immune homeostasis. However, their expansion may impair pathogen elimination and thus may lead to disease persistence [1] . Recently, Shime et al. [2] showed that MDSCs are a target of poly I:C to prime NK cells, which exert antitumor activity to NK-sensitive tumor cells. Staphylococcus aureus is a major human pathogen that was first identified in 1880 by the British surgeon Sir Alexander Ogston in pus from a knee joint abscess [3] . Notably, the mortality of patients with S. aureus bacteremia in the preantibiotic era exceeded 80%, but the introduction of penicillin in the early 1940s dramatically improved the prognosis. However, by the late 1960s, more than 80% of both communityand hospital-acquired staphylococcal isolates were resistant to penicillin. S. aureus cause a diverse array of infections, ranging from less harmful to life threatening. While effective antibiotics against this important pathogen still exist, their number is becoming increasingly limited. Thus, novel approaches to therapy and prevention will become more and more important [4] . In the Published online: January 12, 2015 Journal of Innate Immunity