DESCRIP TION

Staphylococcus aureus is one of the leading causes of bacterial infections worldwide. The pathogenicity and probability of . infection is closely associated with the ability of the host to regulate immunity. Persistent infections are often associated with mutant strains that are less sensitive to antibiotics. However, little is known about how these mutations affect bacterial interactions with the host immune system. Here, the discovery of clinical S. isolate activates human monocytes and the results in cell surface expression of immune stimulatory natural killer group 2D (NKG2D) ligands on the monocytes. Expression of the NKG2D ligand ULBP2 (UL16 binding protein 2) was found to be associated with bacterial degradation and phago lysosome activity. In addition, species induced ULBP2 expression was associated with changes in host cell metabolism, including elevated cytoplasmic (iso) citrate levels, decreased glycolytic flux, and mitochondrial functional activity. Interestingly, the species found the power of ULBP2 and human monocyte inflammatory cytokines are dependent on the functional ClpP protease. These findings indicate that activates ULBP2 in human monocytes an immune metabolic mechanism, indicating that inactivation of clpP may function as a potential antigenic escape mechanism. Our results provide important insights into the interaction between the host immune system and . evolved under the dual evolutionary pressure of host immune response and antibiotic therapy. The discovery of an immune stimulatory pathway consisting of human monocyte-based defense against. suggests that targeting the NKG2D pathway has the potential to treat persistent staphylococcal infections. is an important opportunistic human pathogen distributed around the world. and humans have co-evolved to the point of symbiosis, but the bacteria are endowed with virulence factors that cause catastrophic infections. The adaption of the intracellular lifestages by is an important aspect of its etiology. By occupying the privileged intracellular compartment, the host’s immune and antibiotic bactericidal effects can be avoided. However, this localization exposes to cellular processes that include autophagy, metabolic challenges, and clearance mechanisms coordinated by hosted program cell death pathways (PCDs) such as apoptosis, pyroptosis, and necroptosis. Increased evidence suggests that . employs a pathogenic adaptive mechanism that regulates the expression of its virulence factors to prevent elimination via the PCD pathway. This review critically analyzes the current literature on the interactions between virulence factors and the major interconnect nodes of PCD. We will discuss how . adaptation to human hosts plays an important role in PCD avoidance and consider future directions for studying. PCD interactions.

Submit manuscript at www.walshmedicalmedia.com/submissions/liver.html or send as an e-mail attachment to the liver[at]eclinjournals[dot]com