Highlights d BCG vaccination of humans induces long-term immunophenotypic changes in neutrophils d BCG increases antimicrobial activity of neutrophils against unrelated pathogens d BCG-induced functional changes associate with modifications in histone methylation d Trained immunity may be a therapeutic target in neutrophilmediated diseases

Background: Neutrophil accumulation in the skin is a hallmark of psoriasis. Novel insights on neutrophil phenotypic and functional heterogeneity raise the question to what extent these cells contribute to the sustained inflammatory skin reaction.Objective: We sought to examine the phenotype and functional properties of neutrophils in blood and skin of patients with psoriasis, and the effect of TNF-a and p40(IL-12/IL-23) antibody therapy on circulating neutrophils.

Sepsis is the cause of more than 5.3 million deaths per year, and novel immunotherapeutic strategies are highly warranted. Human models that mirror sepsis immunology are instrumental to this aim. The response to endotoxin in humans during the first 24 hours captures many hallmarks of the inflammatory response observed in sepsis. However, the long-term immunologic effects of human experimental endotoxemia have been sparsely studied and could be determinant for the use of this model in sepsis therapy research. In the present work, we studied the immune-composition of healthy subjects challenged with endotoxin (1 ng/kg) 4 hours, 2 days and 20 days post-administration by flow cytometry to study the effects on innate and adaptive immune system, and compared it with the immune-composition in patients during the first 9 days after onset of septic shock. We found several differences and similarities between these groups. Experimental endotoxemia resulted in an increase in absolute numbers of intermediate monocytes, which also displayed lower HLA-DR expression 20 days post-endotoxin. These changes differed with those observed in septic shock patients. Another long-term effect of experimental endotoxemia was elevated numbers of effector CD8+ cells and an increased percentage of proliferating and cytokine expressing CD8+ cells, and these phenomena were also present in sepsis patients. In conclusion, despite considerable differences, experimental endotoxemia captures several long-term aspects of sepsis immunology, specifically the behavior of CD8 T-cells, which may eventually aid the development of new therapies for sepsis patients.