Effects of <scp>d</scp>-glucosamine and glucose analogues on glycogen biosynthesis <i>in vitro</i>

Kono, Megumi; Quastel, J. H.

doi:10.1042/bj0850024

Cited by 11 publications

(1 citation statement)

References 27 publications

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“…This is likely explained by a limited cellular uptake of GlcNAc even when complexed with transfecting agent or prolonged exposure to increase cytosolic delivery, as previously described ( 44). An important effect of cytosolic GlcNAc is inhibition of glycolysis (44,77). Likewise, we found that the glucose analog 2DG, which is efficiently taken up via glucose transporters and blocks the glycolytic pathway (15,66), significantly increased ULBP2 transcript and surface expression.…”

Section: Discussionmentioning

confidence: 59%

Staphylococcus aureus induces cell-surface expression of immune stimulatory NKG2D ligands on human monocytes

Mellergaard

Høgh

Lund

et al. 2020

Journal of Biological Chemistry

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<s></s>Staphylococcus aureus is among the leading causes of bacterial infections worldwide. The pathogenicity and establishment of S. aureus infections are tightly linked to its ability to modulate host immunity. Persistent infections are often associated with mutant staphylococcal strains that have decreased susceptibility to antibiotics; however, little is known about how these mutations influence bacterial interaction with the host immune system. Here, we discovered that clinical S. aureus isolates activate human monocytes, leading to cell-surface expression of immune stimulatory natural killer group 2D (NKG2D) ligands on the monocytes. We found that expression of the NKG2D ligand UL16-binding protein 2 (ULBP2) is associated with bacterial degradability and phagolysosomal activity. Moreover, S. aureus–induced ULBP2 expression was linked to altered host cell metabolism, including increased cytoplasmic (iso)citrate levels, reduced glycolytic flux, and functional mitochondrial activity. Interestingly, we found that the ability of S. aureus to induce ULBP2 and proinflammatory cytokines in human monocytes depends on a functional ClpP protease in S. aureus. These findings indicate that S. aureus activates ULBP2 in human monocytes through immunometabolic mechanisms and reveal that clpP inactivation may function as a potential immune evasion mechanism. Our results provide critical insight into the interplay between the host immune system and S. aureus that has evolved under the dual selective pressure of host immune responses and antibiotic treatment. Our discovery of a immune stimulatory pathway consisting of human monocyte-based defense against S. aureus suggests that targeting the NKG2D pathway holds potential for managing persistent staphylococcal infections.

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