Intracellular innate immunity and mechanism of action of cytosolic nucleic acid receptor-mediated type I IFN against viruses.

The induction of type I interferons (IFN) is critical for antiviral innate immune response. The rapid activation of antiviral innate immune responses is the key to successful clearance of evading pathogens. To achieve this, a series of proteins, including the pathogen recognition receptors (PRRs), the adaptor proteins, the accessory proteins, kinases, and the transcription factors, are all involved and finely orchestrated. The magnitude and latitude of type I IFN induction however are distinctly regulated in different tissues. A set of interferon simulated genes (ISGs) are then expressed in response to type I IFN signaling to set the cells in the antiviral state. In this review, how type I IFN is induced by viral infections by intracellular PRRs and how type I IFN triggers the expression of downstream effectors will be discussed.

Electrochemical Sensing of Interactions between DNA and Charged Macrocycles

In this work, we investigated aggregation of native DNA and thiacalix[4]arene derivative bearing eight terminal amino groups in cone configuration using various redox probes on the glassy carbon electrode. It was shown that sorption transfer of the aggregates on the surface of the electrode covered with carbon black resulted in changes in electrostatic interactions and diffusional permeability of the surface layer. Such changes alter the signals of ferricyanide ion, methylene green and hydroquinone as redox probes to a degree depending on their specific interactions with DNA and own charge. Inclusion of DNA in the surface layer was independently confirmed by scanning electron microscopy, electrochemical impedance spectroscopy and experiments with doxorubicin as a model intercalator. Thermal denaturing of DNA affected the charge separation on the electrode interface and the signals of redox probes. Using hydroquinone, less sensitive to electrostatic interactions, made it possible to determine from 10 pM to 1.0 nM doxorubicin (limit of detection 3 pM) after 10 min incubation. Stabilizers present in the commercial medications did not alter the signal. The DNA sensors developed can find future application in the assessment of the complexes formed by DNA and macrocycles as delivery agents for small chemical species.

The crosstalk between viral RNA- and DNA-sensing mechanisms.

Viral infections pose a severe threat to humans by causing many infectious, even fatal, diseases, such as the current pandemic disease (COVID-19) since 2019, and understanding how the host innate immune system recognizes viruses has become more important. Endosomal and cytosolic sensors can detect viral nucleic acids to induce type I interferon and proinflammatory cytokines, subsequently inducing interferon-stimulated genes for restricting viral infection. Although viral RNA and DNA sensing generally rely on diverse receptors and adaptors, the crosstalk between DNA and RNA sensing is gradually appreciated. This minireview highlights the overlap between the RNA- and DNA-sensing mechanisms in antiviral innate immunity, which significantly amplifies the antiviral innate responses to restrict viral infection and might be a potential novel target for preventing and treating viral diseases.

The role of extracellular DNA in COVID-19: Clues from inflamm-aging.

Epidemiological data convey severe prognosis and high mortality rate for COVID-19 in elderly men affected by age-related diseases. These subjects develop local and systemic hyper-inflammation, which are associated with thrombotic complications and multi-organ failure. Therefore, understanding SARS-CoV-2 induced hyper-inflammation in elderly men is a pressing need. Here we focus on the role of extracellular DNA, mainly mitochondrial DNA (mtDNA) and telomeric DNA (telDNA) in the modulation of systemic inflammation in these subjects. In particular, extracellular mtDNA is regarded as a powerful trigger of the inflammatory response. On the contrary, extracellular telDNA pool is estimated to be capable of inhibiting a variety of inflammatory pathways. In turn, we underpin that telDNA reservoir is progressively depleted during aging, and that it is scarcer in men than in women. We propose that an increase in extracellular mtDNA, concomitant with the reduction of the anti-inflammatory telDNA reservoir may explain hyper-inflammation in elderly male affected by COVID-19. This scenario is reminiscent of inflamm-aging, the portmanteau word that depicts how aging and aging related diseases are intimately linked to inflammation.