Interferon- γ and infectious diseases: Lessons and prospects

Science, Journal Year: 2024, Volume and Issue: 384(6693)

Published: April 18, 2024

Infectious diseases continue to claim many lives. Prevention of morbidity and mortality from these would benefit not just new medicines vaccines but also a better understanding what constitutes protective immunity. Among the major immune signals that mobilize host defense against infection is interferon-γ (IFN-γ), protein secreted by lymphocytes. Forty years ago, IFN-γ was identified as macrophage-activating factor, and, in recent years, there has been resurgent interest biology its role human defense. Here we assess current IFN-γ, revisit designation an "interferon," weigh prospects therapeutic globally pervasive microbial pathogens.

Language: Английский

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Inducible antibacterial responses in macrophages

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: 25(2), P. 92 - 107

Published: Sept. 18, 2024

Language: Английский

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Honeysuckle‐Derived Carbon Dots With Robust Catalytic and Pharmacological Activities for Mitigating Lung Inflammation by Inhibition of Caspase11/GSDMD‐Dependent Pyroptosis

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Abstract The catalytic activity of carbon dots (CDs) has generated significant interest regarding their potential applications within the biomedical field. However, structure‐activity relationship CDs and pharmacological mechanisms in disease treatment have yet to be comprehensively elucidated. In this study, two distinct types exhibiting superoxide dismutase (SOD)‐like enzymatic activities are synthesized through hydrothermal (Hy‐CDs) carbonization (Ca‐CDs) methods, utilizing Honeysuckle as common material precursor. Through comparative analysis, surface group modifications, theoretical calculations, it is determined that SOD‐like primarily originated from stabilizing influence amino on (•O 2 − ) intermediate its conjugation π‐system, facilitating electron transfer. vitro experiments demonstrated Hy‐CDs effectively alleviated cellular oxidative stress inhibited secretion pro‐inflammatory cytokines. Furthermore, bioactivity properties contribute pronounced therapeutic efficacy acute lung injury (ALI) ischemia/reperfusion (LIRI). Guided by transcriptomic analysis Western blotting, inhibit Caspase11/GSDMD‐dependent non‐classical pyroptosis down‐regulating GBP2 protein expression, thereby contributing inflammation. This study elucidates underlying biological applications.

Language: Английский

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PIM1 controls GBP1 activity to limit self-damage and to guard against pathogen infection

Science, Journal Year: 2023, Volume and Issue: 382(6666)

Published: Oct. 6, 2023

Disruption of cellular activities by pathogen virulence factors can trigger innate immune responses. Interferon-γ (IFN-γ)-inducible antimicrobial factors, such as the guanylate binding proteins (GBPs), promote cell-intrinsic defense attacking intracellular pathogens and inducing programmed cell death. Working in human macrophages, we discovered that GBP1 expression absence IFN-γ killed cells induced Golgi fragmentation. exposure improved macrophage survival through activity kinase PIM1. PIM1 phosphorylated GBP1, leading to its sequestration 14-3-3σ, which thereby prevented membrane association. During

Language: Английский

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Genomic and functional adaptations in guanylate-binding protein 5 (GBP5) highlight specificities of bat antiviral innate immunity

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 15, 2025

Bats are asymptomatic reservoirs of several zoonotic viruses. This may result from long-term coevolution between viruses and bats, that have led to host adaptations contributing an effective balance strong antiviral responses with innate immune tolerance. To better understand these virus-host interactions, we combined comparative transcriptomics, phylogenomics functional assays characterize the evolution bat factors. First, stimulated type I interferon pathway in Myotis yumanensis primary cells identified guanylate-binding protein 5 (GBP5) as most differentially expressed interferon-stimulated gene (ISG). Phylogenomic analyses showed GBP5 has been under episodic positive selection, numerous rapidly evolving sites species-specific duplications, suggesting past evolutionary arms races. Functional tests on orthologs ten species covering >60 million years Chiroptera revealed species- virus-specific restrictions against RNA (retrovirus HIV, rhabdoviruses European lyssavirus VSV), which typical signatures viral epidemics. Interestingly, also observed a lineage-specific loss prenylation motif common ancestor Pipistrellus Eptesicus associated different subcellular localization functions. Resurrection ancestral fuscus rescued its localization, but not complete activities, additional determinants necessary for restriction. Altogether, our results highlight contribute specific immunity provide insights into effector GBP5. is upon stimulation cells. Bat evolved genomic genetic diversification, including early stop codon leading truncation motif.GBP5 diversification bats impacts their functions.Bat GBP5s exhibit virus-specificity ability inhibit infectivity particles, bearing glycoproteins retroviral vesicular stomatitis virus lyssavirus-1.Resurrection rescues full activity.

Language: Английский

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SLICK: A Sandwich-LIke Culturing Kit for in situ Cryo-ET Sample Preparation

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 16, 2025

In situ cryo-electron tomography (cryo-ET) has recently been widely used in observing subcellular structures and macromolecules their native states at high resolution. One of the reasons that it not more adopted by cell biologists structural is difficulties sample preparation. Here we present Sandwich-LIke Culturing Kit (SLICK), simplifying procedure increasing throughput for preparation cryo-ET (69 words).

Language: Английский

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Crystal structures reveal nucleotide-induced conformational changes in G motifs and distal regions in human guanylate-binding protein 2

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Feb. 22, 2025

Guanylate-binding proteins (GBPs) are interferon-inducible GTPases that confer protective immunity against a variety of intracellular pathogens. GBP2 is one the two highly inducible GBPs, yet precise mechanisms underlying activation and regulation GBP2, in particular nucleotide-induced conformational changes remain poorly understood. In this study, we elucidate structural plasticity upon nucleotide binding through crystallographic analysis. By determining crystal structures G domain (GBP2GD) complex with GDP nucleotide-free full-length K51A mutation (GBP2K51A), unveil distinct states adopted by nucleotide-binding pocket distal regions protein. Comparison between GBP2K51A structure homologous reveals notable movement C-terminal helical region, along domain. Through comparative analysis, identify subtle but critical differences nucleotide-bound providing insights into molecular basis its dimer-monomer transition enzymatic activity. These findings pave way for future investigations aimed at elucidating GBP2's role immune response open avenues exploring how unique functions GBPs could be leveraged to combat pathogen invasion. Using biophysical studies, authors provide insight interferon-induced guanylate-binding protein 2. towards new therapeutic strategies overcome

Language: Английский

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New insights into the noncanonical inflammasome point to caspase-4 as a druggable target

Nature reviews. Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Language: Английский

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Versatility of gasdermin D beyond pyroptosis

Trends in Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Type I interferons induce guanylate-binding proteins and lysosomal defense in hepatocytes to control malaria

Cell Host & Microbe, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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