5-Hydroxymethylfurfural
(5-HMF) exists in a wide range of sugar-rich
foods and traditional Chinese medicines. The role of 5-HMF in antiviral
innate immunity and its mechanism have not been reported previously.
In this study, we reveal for the first time that 5-HMF upregulates
the production of retinoic acid-inducible gene I (RIG-I)-mediated
type I interferon (IFN) as a response to viral infection. IFN-β
and IFN-stimulated chemokine gene expressions induced by the vesicular
stomatitis virus (VSV) are upregulated in RAW264.7 cells and primary
peritoneal macrophages after treatment with 5-HMF, a natural product
that appears to inhibit the efficiency of viral replication. Meanwhile,
5-HMF-pretreated mice show enhanced innate antiviral immunity, increased
serum levels of IFN-β, and reduced morbidity and viral loads
upon infection with VSV. Thus, 5-HMF can be seen to have a positive
effect on enhancing type I IFN production. Mechanistically, 5-HMF
upregulates the expression of RIG-I in macrophages, resulting in an
acceleration of the RIG-I signaling pathway activation. Additionally,
STAT1 and STAT2 phosphorylations, along with the expression of IFN-stimulated
chemokine genes induced by IFN-α/β, were also enhanced
in macrophages cotreated with 5-HMF. In summary, these findings indicate
that 5-HMF not only can induce type I IFN production but also can
enhance IFN-JAK/STAT signaling, leading to a novel immunomodulatory
mechanism against viral infection. In conclusion, our study reveals
a previously unrecognized effect of 5-HMF in the antiviral innate
immune response and suggests new potential of utilizing 5-HMF for
controlling viral infection.
Staphylococcus aureus is a major cause of infectious disease. Macrophages can directly destroy most of the invading bacteria through the phagolysosomal pathway. E74‐like factor 4 (Elf4) is one of the important transcription factors that controls diverse pathogens, but the role of Elf4 in macrophage‐mediated S. aureus eradication is unknown. Our data show that Elf4 is induced by S. aureus in macrophages. Elevated expression of Elf4 results in decreased bacterial load and inflammatory responses during S. aureus infection in vivo and in vitro. Elf4‐overexpressed macrophages have decreased mTOR activity and increased lysosomal mass. Collectively, these results suggest that S. aureus induces Elf4 expression, which enhances lysosomal function and increases the capacity of macrophages to eliminate intracellular pathogens.
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