Phase separation as a new form of regulation in innate immunity

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(13), P. 2410 - 2422

Published: June 26, 2024

Language: Английский

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The immune modules conserved across the tree of life: Towards a definition of ancestral immunity

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(7), P. e3002717 - e3002717

Published: July 15, 2024

Immune defence mechanisms exist across the tree of life in such diversity that prokaryotic antiviral responses have historically been considered unrelated to eukaryotic immunity. Mechanisms divergent eukaryotes were similarly believed be largely clade specific. However, recent data indicate a subset modules (domains and proteins) from prokaryote systems are conserved populate many stages innate immune pathways. In this Essay, we propose notion ancestral immunity, which corresponds set between prokaryotes eukaryotes. After offering typology speculate on selective pressures could led differential conservation specific domains life. The exploration immunity is its infancy appears full promises illuminate evolution, also identify decipher economic, ecological, therapeutic importance.

Language: Английский

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Caenorhabditis elegans RIG-I-like receptor DRH-1 signals via CARDs to activate antiviral immunity in intestinal cells

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(29)

Published: July 9, 2024

Upon sensing viral RNA, mammalian RIG-I-like receptors (RLRs) activate downstream signals using caspase activation and recruitment domains (CARDs), which ultimately promote transcriptional immune responses that have been well studied. In contrast, the signaling mechanisms for invertebrate RLRs are much less clear. For example, Caenorhabditis elegans RLR DRH-1 lacks annotated CARDs up-regulates distinct output of RNA interference. Here, we found similar to mammal RLRs, through two tandem (2CARD) induce a response. Expression DRH-1(2CARD) alone in intestine was sufficient gene expression, increase resistance, thermotolerance, phenotype previously associated with C. . We also is required demonstrate subcellular colocalization puncta double-stranded inside cytoplasm intestinal cells upon infection. Altogether, our results reveal mechanistic spatial insights into antiviral , highlighting unexpected parallels between mammals.

Language: Английский

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Phage detection by a bacterial NLR-related protein is mediated by DnaJ

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 4, 2024

Bacteria encode a wide range of antiphage systems and subset these proteins are homologous to components the human innate immune system. Mammalian nucleotide-binding leucine-rich repeat containing (NLRs) bacterial NLR-related use central NACHT domain link infection detection with initiation an antimicrobial response. Bacterial provide defense against both DNA RNA phages. Here we determine mechanism phage by protein bNACHT25 in

Language: Английский

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A bacterial TIR-based immune system senses viral capsids to initiate defense

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 29, 2024

Toll/interleukin-1 receptor (TIR) domains are present in immune systems that protect prokaryotes from viral (phage) attack. In response to infection, TIRs can produce a cyclic adenosine diphosphate-ribose (ADPR) signaling molecule, which activates an effector depletes the host of essential metabolite NAD+ limit phage propagation. How bacterial recognize infection is not known. Here we describe sensing mechanism for staphylococcal Thoeris defense system, consists two TIR domain sensors, ThsB1 and ThsB2, ThsA. We show major capsid protein Φ80α forms complex with sufficient synthesis 1"-3' glycocyclic ADPR (gcADPR) subsequent activation cleavage by Consistent this, phages escape immunity harbor mutations prevent formation. proteins Siphoviridae belonging serogroup B, but A, recognized ThsB1/B2, result suggests recognition Sau-Thoeris other anti-phage may be important evolutionary force behind structural diversity prokaryotic viruses. More broadly, since mammalian toll-like receptors harboring also components inflammatory against our findings reveal conserved innate antiviral pathways.

Language: Английский

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Principles of bacterial innate immunity against viruses

Current Opinion in Immunology, Journal Year: 2024, Volume and Issue: 89, P. 102445 - 102445

Published: Aug. 1, 2024

All organisms must defend themselves against viral predators. This includes bacteria, which harbor immunity factors such as restriction-modification systems and CRISPR-Cas systems. More recently, a plethora of additional defense have been identified, revealing richer, more sophisticated immune system than previously appreciated. Some these newly identified distant homologs in mammals, suggesting an ancient evolutionary origin some facets mammalian immunity. An even broader conservation exists at the level how operate. Here, we focus this level, reviewing key principles high-level attributes innate bacteria that are shared with immunity, while also noting differences, particular emphasis on cells sense infection.

Language: Английский

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Animal and bacterial viruses share conserved mechanisms of immune evasion

Cell, Journal Year: 2024, Volume and Issue: 187(20), P. 5530 - 5539.e8

Published: Aug. 27, 2024

Language: Английский

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Immunoinformatics design of a novel multiepitope vaccine candidate against non-typhoidal salmonellosis caused by Salmonella Kentucky using outer membrane proteins A, C, and F

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0306200 - e0306200

Published: Jan. 10, 2025

The global public health risk posed by Salmonella Kentucky ( S . Kentucky) is rising, particularly due to the dissemination of antimicrobial resistance genes in human and animal populations. This serovar, widespread Africa, has emerged as a notable cause non-typhoidal gastroenteritis humans. In this study, we used bioinformatics approach develop peptide-based vaccine targeting epitopes from outer membrane proteins A, C, F Kentucky. Additionally, employed flagellin protein fliC ) Typhimurium Typhimurium) an adjuvant enhance vaccine’s effectiveness. Through approach, identified 14 CD8+ 7 CD4+ T-cell epitopes, which are predicted be restricted various MHC class I II alleles. expected achieve population coverage 94.91% when formulations. Furthermore, seven highly immunogenic linear B-cell three conformational epitopes. These were then linked using appropriate linkers create multi-epitope (MEV). To boost immunogenicity peptide construct, was included at N-terminal. resulting MEV construct demonstrated high structural quality favorable physicochemical properties. Molecular docking studies with Toll-like receptors 1, 2, 4, 5, followed molecular dynamic simulations, suggested that vaccine-receptor complexes energetically feasible, stable, robust. Immune simulation results showed elicited significant responses, including IgG, IgM, T-cells, cytokines (IFN-γ, TGF-β, IL-2, IL-10, IL-12), along noticeable reduction antigen levels. Despite these promising in-silico findings, further validation through preclinical clinical trials required confirm efficacy safety.

Language: Английский

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Self-sacrificing cell death to thwart phage infection

Nature Reviews Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Language: Английский

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Pseudomonads coordinate innate defense against viruses and bacteria with a single regulatory system

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

Published: Feb. 27, 2025

Bacterial cells live under the constant existential threats imposed by other bacteria and viruses. Their mechanisms for contending with these are well documented; however, regulation of diverse defense elements remains poorly understood. Here we show that can mount a genome-wide, coordinated, highly effective immune response against bacterial viral using single regulatory pathway. Bioinformatic analyses revealed Pseudomonas species broadly possess specialized form Gac/Rsm pathway (GRP), which our prior work in aeruginosa implicated activating interbacterial antagonism to neighbor cell death. Proteomic studies comparing GRP-activated -inactivated strains derived from showed regulates large variable suite factors both phage threats. Focusing on P. protegens, identify profound phenotypic consequences multiple forms several phage. Together, results reveal bacteria, like more complex organisms, couple danger sensing activation an system antibacterial antiviral arms.

Language: Английский

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