Staphylococcus aureus and the Cutaneous Microbiota Biofilms in the Pathogenesis of Atopic Dermatitis

Biofilm is the dominant mode of growth of the skin microbiota, which promotes adhesion and persistence in the cutaneous microenvironment, thus contributing to the epidermal barrier function and local immune modulation. In turn, the local immune microenvironment plays a part in shaping the skin microbiota composition. Atopic dermatitis (AD) is an immune disorder characterized by a marked dysbiosis, with a sharp decline of microbial diversity. During AD flares biofilm-growing Staphylococcus aureus emerges as the major colonizer in the skin lesions, in strict association with disease severity. The chronic production of inflammatory cytokines in the skin of AD individuals concurs at supporting S. aureus biofilm overgrowth at the expense of other microbial commensals, subverting the composition of the healthy skin microbiome. The close relationship between the host and microbial biofilm resident in the skin has profound implications on human health, making skin microbiota an attractive target for the therapeutic management of different skin disorders.

Recombinant protein rMBP-NAP restricts tumor progression by triggering antitumor immunity in mouse metastatic lung cancer

Recombinant Helicobacter pylori neutrophil-activating protein fused with maltose-binding protein (rMBP-NAP), a potential TLR2 ligand, was reported to possess immunomodulatory effects on in situ tumors in our previous study. In the present work, we attempt to elucidate the effect of rMBP-NAP at the local immune modulation in B16-F10-induced metastatic lung cancer. Our results demonstrated that growth of B16-F10 melanoma metastases in the lung was significantly arrested after rMBP-NAP treatment, along with marked reduction in metastatic lung nodules and significant increase in survival. The treatment induced both local and systemic immune responses, which were associated with higher influx of CD4+/CD8+ T cells and drove toward Th1-like and cytotoxic immune environment. Moreover, rMBP-NAP also showed significant anti-angiogenic activity by reducing vascularization in lung tumor sections. rMBP-NAP could induce antitumor immunity through activating Th1 cells and producing pro-inflammatory cytokines, which are responsible for the effective cytotoxic immune response against cancer progression. Our findings indicate that rMBP-NAP might be a novel antitumor therapeutic strategy.

Blastocyst metabolism

The mammalian blastocyst exhibits an idiosyncratic metabolism, reflecting its unique physiology and its ability to undergo implantation. Glucose is the primary nutrient of the blastocyst, and is metabolised both oxidatively and through aerobic glycolysis. The production of significant quantities of lactate by the blastocyst reflects specific metabolic requirements and mitochondrial regulation; it is further proposed that lactate production serves to facilitate several key functions during implantation, including biosynthesis, endometrial tissue breakdown, the promotion of new blood vessel formation and induction of local immune-modulation of the uterine environment. Nutrient availability, oxygen concentration and the redox state of the blastocyst tightly regulate the relative activities of specific metabolic pathways. Notably, a loss of metabolic normality is associated with a reduction in implantation potential and subsequent fetal development. Even a transient metabolic stress at the blastocyst stage culminates in low fetal weights after transfer. Further, it is evident that there are differences between male and female embryos, with female embryos being characterised by higher glucose consumption and differences in their amino acid turnover, reflecting the presence of two active X-chromosomes before implantation, which results in differences in the proteomes between the sexes. In addition to the role of Hypoxia-Inducible Factors, the signalling pathways involved in regulating blastocyst metabolism are currently under intense analysis, with the roles of sirtuins, mTOR, AMP-activated protein kinase and specific amino acids being scrutinised. It is evident that blastocyst metabolism regulates more than the production of ATP; rather, it is apparent that metabolites and cofactors are important regulators of the epigenome, putting metabolism at centre stage when considering the interactions of the blastocyst with its environment.