Liquid-liquid phase separation in innate immunity.

Intrinsic and innate immune responses are essential lines of defense in the body's constant surveillance of pathogens. The discovery of liquid-liquid phase separation (LLPS) as a key regulator of this primal response to infection brings an updated perspective to our understanding of cellular defense mechanisms. Here, we review the emerging multifaceted role of LLPS in diverse aspects of mammalian innate immunity, including DNA and RNA sensing and inflammasome activity. We discuss the intricate regulation of LLPS by post-translational modifications (PTMs), and the subversive tactics used by viruses to antagonize LLPS. This Review, therefore, underscores the significance of LLPS as a regulatory node that offers rapid and plastic control over host immune signaling, representing a promising target for future therapeutic strategies.

Differential Contributions of Interferon Classes to Host Inflammatory Responses and Restricting Virus Progeny Production.

Fundamental to mammalian intrinsic and innate immune defenses against pathogens is the production of Type I and Type II interferons, such as IFN-ß and IFN-γ, respectively. The comparative effects of IFN classes on the cellular proteome, protein interactions, and virus restriction within cell types that differentially contribute to immune defenses are needed for understanding immune signaling. Here, a multilayered proteomic analysis, paired with biochemical and molecular virology assays, allows distinguishing host responses to IFN-ß and IFN-γ and associated antiviral impacts during infection with several ubiquitous human viruses. In differentiated macrophage-like monocytic cells, we classified proteins upregulated by IFN-ß, IFN-γ, or pro-inflammatory LPS. Using parallel reaction monitoring, we developed a proteotypic peptide library for shared and unique ISG signatures of each IFN class, enabling orthogonal confirmation of protein alterations. Thermal proximity coaggregation analysis identified the assembly and maintenance of IFN-induced protein interactions. Comparative proteomics and cytokine responses in macrophage-like monocytic cells and primary keratinocytes provided contextualization of their relative capacities to restrict virus production during infection with herpes simplex virus type-1, adenovirus, and human cytomegalovirus. Our findings demonstrate how IFN classes induce distinct ISG abundance and interaction profiles that drive antiviral defenses within cell types that differentially coordinate mammalian immune responses.

IFI16 phase separation via multi-phosphorylation drives innate immune signaling.

The interferon inducible protein 16 (IFI16) is a prominent sensor of nuclear pathogenic DNA, initiating innate immune signaling and suppressing viral transcription. However, little is known about mechanisms that initiate IFI16 antiviral functions or its regulation within the host DNA-filled nucleus. Here, we provide in vitro and in vivo evidence to establish that IFI16 undergoes liquid-liquid phase separation (LLPS) nucleated by DNA. IFI16 binding to viral DNA initiates LLPS and induction of cytokines during herpes simplex virus type 1 (HSV-1) infection. Multiple phosphorylation sites within an intrinsically disordered region (IDR) function combinatorially to activate IFI16 LLPS, facilitating filamentation. Regulated by CDK2 and GSK3ß, IDR phosphorylation provides a toggle between active and inactive IFI16 and the decoupling of IFI16-mediated cytokine expression from repression of viral transcription. These findings show how IFI16 switch-like phase transitions are achieved with temporal resolution for immune signaling and, more broadly, the multi-layered regulation of nuclear DNA sensors.

Dual modification based on electrostatic repulsion of bentonite and SPR effect of Bi facilitate charge transfer of Bi2WO6 for antibiotics degradation.

Development of efficient photocatalysts is vital for light-driven removal of refractory antibiotics. Herein, Bi2WO6 microspheres were successfully anchored on the surface of bentonite, and metallic Bi was reduced in-situ by a one-step solvothermal method. Notably, the Bi/Bi2WO6/BT with a mass ratio of 0.15:1:0.1 exhibited the best photocatalytic activity toward degradation of tetracycline (TC) and ciprofloxacin (CIP) after 120 min of visible light irradiation, and their reaction rate constants were 8.0 and 5.5 folds higher than that of pristine Bi2WO6, respectively. The boosted photocatalytic activity over Bi/Bi2WO6/BT was ascribed to the establishment of electrostatic repulsion and SPR effect, which synergistically promoted charges transfer, thus achieving more h+ and ·O2- radical generation. Moreover, possible TC and CIP degradation pathways over Bi/Bi2WO6/BT were proposed based on the identified intermediates, and most of the intermediates were less toxic than TC and CIP. The study provides options to develop high-efficiency photocatalytic composites for contaminants elimination using semiconductors and readily available bentonite.

Visible light driven antibiotics degradation using S-scheme Bi2WO6/CoIn2S4 heterojunction: Mechanism, degradation pathways and toxicity assessment.

S-scheme heterojunction photocatalysts with strong redox ability and excellent photocatalytic activity are highly desired for photocatalytic degradation of pollutants. Herein, S-scheme Bi2WO6/CoIn2S4 heterojunctions were synthesized using hydrothermal method. The photo-induced carriers transfer mechanism of the S-scheme Bi2WO6/CoIn2S4 heterojunction was clarified by band structure analysis, ultraviolet photoelectron spectrometer (UPS), electron spin resonance (ESR) and radical trapping experiments. Significant enhance of light absortion, and more efficient carriers separation were observed from the Bi2WO6/CoIn2S4 with CoIn2S4 nanoclusters growing on the surface of petal-like Bi2WO6 nanosheets. TC degradation efficiency of 90% was achieved by Bi2WO6/CoIn2S4 (15:1) within 3 h of irradiation, and ·O2-and ·OH radicals were dominated contributors. Possible decomposition pathways of TC were proposed, and ECOSAR analysis showed that most of the intermediates exhibited lower ecotoxicity than TC. This work provides reference on the constructing ternary-metal-sulfides-based S-scheme heterojunctions for improving photocatalytic performance.

Step-doped disulfide vacancies and functional groups synergistically enhance photocatalytic activity of S-scheme Cu3SnS4/L-BiOBr towards ciprofloxacin degradation.

Development of efficient photocatalysts for efficient recalcitrant organic pollutants degradation is of great significance. Herein, the step-doped disulfide vacancies S-scheme Cu3SnS4/L-BiOBr (CTS/L-BiOBr) heterojunction photocatalyst was prepared for ciprofloxacin (CIP) degradation. X-ray photoelectron spectroscopy (XPS) analysis, ultraviolet photo-electron spectroscopy (UPS) analysis, band structure and dominant radicals' identification together verified that the transfer of photogenerated carriers conformed to the S-scheme mechanism. Benefited from the interfacial electric field (IEF) of the S-scheme heterojunction and incorporation of L-cysteine with introducing S-vacancies and surface functional groups (-NH2, -COO-), photogenerated charges generation and separation of the CTS/L-BiOBr(10) were greatly improved. With ·OH and h+ as dominant reactive species, CIP removal reached 93% using CTS/L-BiOBr(10) within 180 min of visible light irradiation, which was 3.5 times and 2.6 times of pristine Cu3SnS4 and L-BiOBr, respectively. Moreover, possible CIP degradation pathways were proposed and the degradation intermediates ecotoxicity were evaluated. This study could provide reference for designing efficient S-scheme photocatalysts for recalcitrant wastewater treatment.