Effector-Triggered Immunity

Annual Review of Immunology, Год журнала: 2023, Номер 41(1), С. 453 - 481

Опубликована: Фев. 8, 2023

The innate immune system detects pathogens via germline-encoded receptors that bind to conserved pathogen ligands called pathogen-associated molecular patterns (PAMPs). Here we consider an additional strategy of sensing effector-triggered immunity (ETI). ETI involves detection pathogen-encoded virulence factors, also effectors. Pathogens produce effectors manipulate hosts create a replicative niche and/or block host immunity. Unlike PAMPs, are often diverse and rapidly evolving can thus be unsuitable targets for direct by receptors. Effectors instead sensed indirectly their activities. is viable used across phyla, including plants, but the mechanisms complex compared simple receptor/ligand-based PAMP detection. survey functions ETI, with particular focus on emerging insights from animal studies. We suggest many examples may remain discovered, hiding in plain sight throughout immunology.

Язык: Английский

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A host of armor: Prokaryotic immune strategies against mobile genetic elements

Cell Reports, Год журнала: 2023, Номер 42(7), С. 112672 - 112672

Опубликована: Июнь 21, 2023

Prokaryotic adaptation is strongly influenced by the horizontal acquisition of beneficial traits via mobile genetic elements (MGEs), such as viruses/bacteriophages and plasmids. However, MGEs can also impose a fitness cost due to their often parasitic nature differing evolutionary trajectories. In response, prokaryotes have evolved diverse immune mechanisms against MGEs. Recently, our understanding abundance diversity prokaryotic systems has greatly expanded. These defense degrade invading material, inhibit genome replication, or trigger abortive infection, leading population protection. this review, we highlight these strategies, focusing on most recent discoveries. The study defenses not only sheds light microbial evolution but uncovers novel enzymatic activities with promising biotechnological applications.

Язык: Английский

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Cryo-EM structure of the RADAR supramolecular anti-phage defense complex

Cell, Год журнала: 2023, Номер 186(5), С. 987 - 998.e15

Опубликована: Фев. 9, 2023

RADAR is a two-protein bacterial defense system that was reported to defend against phage by "editing" messenger RNA. Here, we determine cryo-EM structures of the complex, revealing RdrA as heptameric, two-layered AAA+ ATPase and RdrB dodecameric, hollow complex with twelve surface-exposed deaminase active sites. join form giant assembly up 10 MDa, docked funnel over site. Surprisingly, our reveal an site targets mononucleotides. We show catalyzes ATP-to-ITP conversion in vitro induces massive accumulation inosine mononucleotides during infection vivo, limiting replication. Our results define ATP mononucleotide deamination determinant immunity supramolecular nucleotide-modifying machine mechanism anti-phage defense.

Язык: Английский

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SAMHD1 Modulates Early Steps during Human Cytomegalovirus Infection by Limiting NF-κB Activation

Cell Reports, Год журнала: 2019, Номер 28(2), С. 434 - 448.e6

Опубликована: Июль 1, 2019

Highlights•HCMV infection induces SAMHD1 expression and phosphorylation•SAMHD1 restricts HCMV gene before virus replication•SAMHD1 deficiency limits entry into the quiescent stage of infection•HCMV restriction by is mediated limiting NF-κB activationSummaryCellular inhibits replication many viruses intracellular deoxynucleoside triphosphate (dNTP) pools. We investigate influence on human cytomegalovirus (HCMV). During infection, we observe induction, accompanied phosphorylation via viral kinase UL97. depletion increases in permissive fibroblasts conditionally myeloid cells. show this due to enhanced from major immediate-early (MIE) promoter independent dNTP levels. suppresses innate immune responses inhibiting nuclear factor κB (NF-κB) activation. that regulates MIE through Chromatin immunoprecipitation reveals increased RELA RNA polymerase II absence SAMHD1. Our studies reveal a mechanism how activates an pathway paradoxically results transcriptional activation promoter.Graphical abstract

Язык: Английский

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Regulation and function of the cGAS-MITA/STING axis in health and disease

Cell Insight, Год журнала: 2022, Номер 1(1), С. 100001 - 100001

Опубликована: Янв. 21, 2022

The innate immune systems detect pathogens via pattern-recognition receptors including nucleic acid sensors and non-nucleic sensors. Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS, also known as MB21D1) is a cytosolic DNA sensor that recognizes double-stranded (dsDNA) catalyzes the synthesis of 2′,3′-cGAMP. Subsequently, 2′,3′-cGAMP binds to adaptor protein mediator IRF3 activation (MITA, STING, MPYS, ERIS, TMEM173) activate downstream signaling cascades. cGAS-MITA/STING critically mediates responses against viruses, retroviruses, bacteria, protozoan parasites. In addition, recent discoveries have extended our understanding roles pathway in autoimmune diseases cancers. Here, we summarize identification cGAS MITA/STING, present updated functions regulatory mechanisms provide comprehensive axis

Язык: Английский

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Similarities in the induction of the intracellular pathogen response in Caenorhabditis elegans and the type I interferon response in mammals

BioEssays, Год журнала: 2023, Номер 45(11)

Опубликована: Сен. 4, 2023

Although the type-I interferon (IFN-I) response is considered vertebrate-specific, recent findings about Intracellular Pathogen Response (IPR) in nematode Caenorhabditis elegans indicate that there are similarities between these two transcriptional immunological programs. The IPR induced during infection with natural intracellular fungal and viral pathogens of intestine promotes resistance against pathogens. Similarly, IFN-I by viruses other infection. Whether evolved a divergent or convergent manner an unanswered exciting question, which could be addressed further studies immunity C. simple host organisms. Here we highlight similar roles played RIG-I-like receptors, purine metabolism enzymes, proteotoxic stressors, transcription factors to induce response, as well consequences defense programs on organismal development.

Язык: Английский

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Nucleic acid triggers of autoimmunity and autoinflammation

Current Opinion in Immunology, Год журнала: 2025, Номер 93, С. 102535 - 102535

Опубликована: Янв. 30, 2025

Язык: Английский

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Integrated Approach for Biomarker Discovery and Mechanistic Insights into the Co-Pathogenesis of Type 2 Diabetes Mellitus and Non-Hodgkin Lymphoma

Diabetes Metabolic Syndrome and Obesity, Год журнала: 2025, Номер Volume 18, С. 267 - 282

Опубликована: Янв. 1, 2025

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of non-Hodgkin lymphoma (NHL), but the underlying mechanisms remain unclear. This study aimed to identify potential biomarkers and elucidate molecular co-pathogenesis T2DM NHL. Microarray datasets NHL were downloaded from Gene Expression Omnibus database. Subsequently, a protein-protein interaction network was constructed based on common differentially expressed genes (DEGs) between explore regulatory interactions. Functional analyses performed mechanisms. Topological analysis machine learning algorithms applied refine hub gene selection. Finally, quantitative real-time polymerase chain reaction validate in clinical samples. Intersection DEGs identified 81 shared genes. suggested that immune-related pathways played significant role three genes: GZMM, HSPG2, SERPING1. Correlation revealed correlations these immune cells, underscoring importance dysregulation pathogenesis. The expression successfully validated pivotal as key contributors. These findings provide insight into complex interplay

Язык: Английский

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De-ubiquitination of SAMHD1 by USP7 promotes DNA damage repair to overcome oncogenic stress and affect chemotherapy sensitivity

Oncogene, Год журнала: 2023, Номер 42(22), С. 1843 - 1856

Опубликована: Апрель 20, 2023

Abstract Oncogenic stress induces DNA damage repair (DDR) that permits escape from mitotic catastrophe and allows early precursor lesions during the evolution of cancer. SAMHD1, a dNTPase protecting cells viral infections, has been recently found to participate in process. However, its role tumorigenesis remains largely unknown. Here, we show SAMHD1 is up-regulated early-stage human carcinoma tissues cell lines under oxidative or genotoxic insults. We further demonstrate de-ubiquitinating enzyme USP7 interacts with de-ubiquitinates it at lysine 421, thus stabilizing protein expression for interaction CtIP DDR, which promotes tumor survival stress. Furthermore, levels positively correlates various carcinomas, associated an unfavorable outcome patients who underwent chemotherapy. Moreover, inhibitor sensitizes chemotherapeutic agents by decreasing vitro vivo. These findings suggest de-ubiquitination DDR overcome oncogenic affect chemotherapy sensitivity.

Язык: Английский

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Leukodystrophy Imaging: Insights for Diagnostic Dilemmas

Medical Sciences, Год журнала: 2024, Номер 12(1), С. 7 - 7

Опубликована: Янв. 25, 2024

Leukodystrophies, a group of rare demyelinating disorders, mainly affect the CNS. Clinical presentation different types leukodystrophies can be nonspecific, and thus, imaging techniques like MRI used for more definitive diagnosis. These diseases are characterized as cerebral lesions with characteristic patterns which differentiating tools. In this review, we talk about these study findings each leukodystrophy, associated genetics, blood work that help in differentiation, emerging diagnostics, follow-up strategy. The discussed paper include X-linked adrenoleukodystrophy, metachromatic Krabbe’s disease, Pelizaeus–Merzbacher Alexander’s Canavan Aicardi–Goutières Syndrome.

Язык: Английский

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