Extracellular Vesicles Derived from Plasmodium-infected Hosts as Stimuli of "Trained" Innate Immunity.

Although the burden of malaria has been successfully controlled globally, this disease remains a major public health issue. To date, neither existing drugs nor vaccines against malaria are sufficient in eliminating malaria worldwide. To achieve the eradication of malaria by 2040, effective interventions targeting all Plasmodium species are urgently needed. As the cornerstone of vaccine design, immune memory serves a significant role in the host's defense against Plasmodium infections. It has long been considered that innate immunity is non-specific and lacks immunologic memory. However, emerging evidence has suggested that innate immunity can be trained following exposure of the body to infectious agents, such as Plasmodium or its products, which, in turn, promotes the onset of a type of memory in innate immune cells. The above "trained" innate immune cells, whose phenotype is modified in response to epigenetic modifications, metabolic recombination, or cytokine secretion, exhibit differential pathophysiology after the exposure of the body to a pathogen. In addition, Plasmodium-infected red blood cells and other host cells can secrete exosomes that contain conserved parasite-specific information, such as proteins, RNA, non-coding RNA molecules, and nucleic acids. These molecules can act as stimuli for promoting the establishment of "trained" innate immunity against malaria, thereby altering the onset and progression of the parasitic disease. A deeper understanding of the role of exosomes in the development of "trained" innate immunity during Plasmodium infection could provide novel therapeutic and prevention strategies against malaria infections.

Silencing KRT16 inhibits keratinocyte proliferation and VEGF secretion in psoriasis via inhibition of ERK signaling pathway.

Psoriasis is a multisystem disease affecting about 2% of the population, while keratin16 (KRT16) has been reported to participate in psoriasis. However, the specific mechanism of KRT16 in psoriasis was inadequately investigated. The objective of the study was to elucidate the mechanism by which siRNA-mediated silencing of KRT16 affects keratinocyte proliferation and vascular endothelial growth factor (VEGF) secretion in psoriasis through the extracellular signal-related kinase (ERK) signaling pathway. Psoriasis-related core gene KRT16 was screened out. Then, the expression of KRT16, VEGF, and ERK signaling pathway-related genes was detected in psoriatic patients. To further investigate the mechanism of KRT16, keratinocytes in psoriatic patients were treated with KRT16 siRNA or/and ERK inhibitor (PD98059) to detect the changes in related gene expression and cell survival. KRT16 was involved in psoriasis development. The expression levels of KRT16, p-ERK1/2, and VEGF in lesion tissues are significantly elevated. Keratinocytes treated with KRT16-siRNA and KRT16-siRNA + PD98059 exhibited reduced KRT16, p-ERK1/2, and VEGF expression. The cell survival rate in cells treated with KRT16-siRNA, PD98059, and KRT16-siRNA + PD98059 reduced significantly. These findings indicate that silencing KRT16 inhibits keratinocyte proliferation and VEGF secretion in psoriasis via inhibition of ERK signaling pathway, which provides a basic theory in the treatment of psoriasis.