Enterococcus faecalis, a Gram-positive opportunistic pathogen having lipoteichoic acid (LTA) as a major virulence factor, is closely associated with refractory apical periodontitis. Short-chain fatty acids (SCFAs) are found in the apical lesion and may affect inflammatory responses induced by E. faecalis.
View Article and Find Full Text PDFAs an enveloped virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delivers its viral genome into host cells via fusion of the viral and cell membranes. Here, we show that ANO6/TMEM16F-mediated cell surface exposure of phosphatidylserine is critical for SARS-CoV-2 entry and that ANO6-selective inhibitors are effective against SARS-CoV-2 infections. Application of the SARS-CoV-2 Spike pseudotyped virus (SARS2-PsV) evokes a cytosolic Ca elevation and ANO6-dependent phosphatidylserine externalization in ACE2/TMPRSS2-positive mammalian cells.
View Article and Find Full Text PDFUnder ER stress conditions, the ER form of transmembrane proteins can reach the plasma membrane via a Golgi-independent unconventional protein secretion (UPS) pathway. However, the targeting mechanisms of membrane proteins for UPS are unknown. Here, this study reports that TMED proteins play a critical role in the ER stress-associated UPS of transmembrane proteins.
View Article and Find Full Text PDFThe most prevalent pathogenic mutations in the (Δ) and /pendrin (), which cause cystic fibrosis and congenital hearing loss, respectively, evoke protein misfolding and subsequent defects in their cell surface trafficking. Here, we report that activation of the IRE1α kinase pathway can rescue the cell surface expression of ΔF508-CFTR and p.H723R-pendrin through a Golgi-independent unconventional protein secretion (UPS) route.
View Article and Find Full Text PDFShort-chain fatty acids (SCFAs), such as acetate, butyrate, and propionate, modulate immune responses in the gut. However, the effect of SCFAs on mucosal vaccine-induced immune cell migration is poorly understood. Here, we investigated whether SCFAs modulate chemokine expression induced by the killed whole-cell oral cholera vaccine, Shanchol™, in human intestinal epithelial cells.
View Article and Find Full Text PDFLipoteichoic acid (LTA), a major cell wall component of Gram-positive bacteria, is associated with various inflammatory diseases ranging from minor skin diseases to severe sepsis. It is known that LTA is recognized by Toll-like receptor 2 (TLR2), leading to the initiation of innate immune responses and further development of adaptive immunity. However, excessive immune responses may result in the inflammatory sequelae that are involved in severe diseases such as sepsis.
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