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Tissier, A.

Publications and source records attributed to Tissier, A..

7 recordsLinked to original sources

CRY-NLRP3 complexes define a circadian checkpoint controlling inflammasome activation

Innate immune sensors such as the NLRP3 inflammasome can trigger inflammatory responses within minutes, raising the question of how circadian clocks influence such rapid decisions. Here, we identify a protein-level circadian checkpoint that links core clock components to NLRP3 inflammasome activation. We show that NLRP3 associates with the circadian repressors CRY1 and CRY2, forming oscillatory complexes that restrain inflammasome activation and rapidly dissociate upon stimulation. Pharmacological stabilization of CRY proteins preserves CRY-NLRP3 association and attenuates inflammasome assembly, IL-1{beta} secretion and pyroptotic cell death in primary human macrophages. In synchronized macrophages, both NLRP3 inflammasome activation and its inhibition by the NLRP3 inhibitor MCC950 vary with circadian time. Finally, a subset of NLRP3 variants reported in cohorts of patients with Cryopyrin-Associated Periodic Syndromes (CAPS), a group of hereditary fever syndromes caused by mutations in NLRP3, weaken CRY binding and are associated with altered time-of-day patterns of inflammasome activation and MCC950 responsiveness. Together, these findings define CRY-NLRP3 complexes as a circadian checkpoint that modulates inflammasome activity and drug response, revealing time of day as a critical dimension of NLRP3-driven inflammation.

immunology↗

Cooperation between a root fungal endophyte and host-derived coumarin scopoletin mediates Arabidopsis iron nutrition

O_LIIron acquisition is a critical challenge for plants, especially in iron-deficient soils. Recent research underscores the importance of root-exuded coumarins in modulating the root microbiome community structure and facilitating iron uptake. However, interactions between root-associated fungi and coumarins in plant iron nutrition remain unknown. We investigated the mechanism by which a fungal endophyte, Macrophomina phaseolina (F80), enhances Arabidopsis iron nutrition. C_LIO_LIFungal-coumarin interactions were assessed by profiling metabolites and measuring iron mobilisation in F80 cultures supplemented with specific coumarins, alongside quantifying growth performance and iron content in Arabidopsis coumarin-biosynthesis mutants inoculated with F80. C_LIO_LIOur findings reveal that an interaction between the coumarin scopoletin and F80 in the rhizosphere rescues plant growth under iron-limiting conditions by resolving the iron mobility bottleneck. F80 exhibits a capacity to modify scopoletin into iron-chelating catechol coumarin esculetin, thereby releasing available iron. C_LIO_LIWe conclude that Arabidopsis-produced scopoletin functions as a precursor for fungal conversion into iron-chelating coumarins. By extending the role of coumarins from bacterial to fungal members of the root microbiota, this study places coumarins at the centre of commensal-mediated enhancement of plant iron nutrition across microbial kingdoms. C_LI

plant biology↗

The inflammasome sensor NLRP3 interacts with REV7 to maintain genome integrity through homologous recombination

DNA double strand break (DSB) is a highly toxic lesion that can generate genome instability, a major source of tumorigenesis. DSBs are mainly repaired by non-homologous end joining (NHEJ) or homologous recombination (HR). The selection of the DSB repair pathway primarily depends on the DNA resection of the DSB ends. Indeed, HR is initiated by resection at the DSB generating 3 single stranded extension. The shieldin complex prevents resection fostering DSB repair toward NHEJ. Here, we reveal that the inflammasome sensor NLRP3 facilitates DNA end resection to promote the HR pathway in an inflammasome-independent manner. Strikingly, NLRP3 silencing decreases HR efficiency, as evidenced by RAD51 foci and functional HR assays. Mechanistically, we describe that NLRP3 interacts with REV7, a subunit of the shieldin complex, and its depletion increases REV7 recruitment to IR-induced DSBs. Similar to cancer cells harboring HR mutated genes, we find that NLRP3 deficient cells are sensitive to PARP inhibitors (PARPi) and exhibit an epistatic relationship with BRCA1 deficiency. Remarkably, loss of REV7 in NLRP3-depleted cells induces PARPi resistance by restoring HR. This study unravels the crucial role of the innate immune receptor NLRP3 in regulating the selection of DSB repair pathways to maintain genome integrity.

molecular biology↗

The Arabidopsis Concert of Metabolic Acclimation to High Light Stress

In plants, exposure to high light irradiation induces various stress responses, which entail complex metabolic rearrangements. To systematically study such dynamic changes, we conducted time course experiments from 2 minutes to 72 hours with Arabidopsis thaliana plants exposed to high and control light conditions. We performed comparative metabolomics, transcriptomics, redox proteomics and stable isotope labelling on leaf rosettes. Our data analysis identifies a set of synchronous and successive responses that provide a deeper insight into well-orchestrated mechanisms contributing to high light acclimation. We observe a downregulation of genes encoding light harvesting proteins and a transient restriction of genes involved in linear electron flow through photosystem I. C4 acids, produced via anaplerotic routes, strongly accumulate under high light conditions. Redox homeostasis is tightly balanced by reduced NADPH production, enhanced subcellular redistribution of reducing equivalents across several subcellular compartments via photorespiration and activation of processes that quench reactive oxygen species. In this well-orchestrated network, methylerythritol 2,4-cyclodiphosphate, fulfills a dual function as intermediate of plastidic isoprenoid production and as a stress signal molecule.

plant biology↗

Auxin-dependent acceleration of cell division rates regulates root growth at elevated temperature

Roots are highly plastic organs enabling plants to acclimate to a changing below-ground environment. In addition to abiotic factors like nutrients or mechanical resistance, plant roots also respond to temperature variation. Below the heat stress threshold, Arabidopsis thaliana seedlings react to elevated temperature by promoting primary root growth, possibly to reach deeper soil regions with potentially better water saturation. While above-ground thermomorphogenesis is enabled by thermo-sensitive cell elongation, it was unknown how temperature modulates root growth. We here show that roots are able to sense and respond to elevated temperature independent of shoot-derived signals. A yet unknown root thermosensor seems to employ auxin as a messenger to promote primary root growth. Growth is primarily achieved by accelerating cell division rates in the root apical meristem, likely maintained via temperature-sensitive organization of the polar auxin transport system. Hence, the primary cellular target of elevated ambient temperature differs fundamentally between root and shoot tissues, while the messenger auxin that relays temperature information to elongating or dividing cells, respectively, remains the same.

plant biology↗

Introgression of type-IV glandular trichomes from Solanum galapagense to cultivated tomato reveals genetic complexity for the development of acylsugar-based insect resistance

Glandular trichomes are involved in the production of food- and medicine-relevant chemicals in plants, besides being associated with pest resistance. In some wild Solanum species closely related to the cultivated tomato (S. lycopersicum), the presence of type-IV glandular trichomes leads to the production of high levels of insecticide acylsugars (AS). Conversely, low AS production observed in the cultivated tomato is attributed to its incapacity to develop type-IV trichomes in adult organs. Therefore, we hypothesized that cultivated tomatoes engineered to harbor type-IV trichomes on the leaves of mature plants can be pest resistant. We introgressed into the tomato cultivar Micro-Tom (MT) the capability of S. galapagense to maintain the development of type-IV trichomes throughout all plant stages, thus creating a line named "Galapagos enhanced trichomes" (MT-Get). Mapping-by-sequencing of MT-Get revealed that five chromosomal regions of S. galapagense were present in MT-Get. Further mapping reveled that S. galapagense alleles on chromosomes 1, 2 and 3 are sufficient for the presence of type-IV trichomes, but in lower densities. GC-MS, LC-MS, and gene expression analyses demonstrated that the increased density of type-IV trichomes was not accompanied by high AS production and exudation in MT-Get. Moreover, MT-Get did not differ from MT in its susceptibility to whitefly (Bemisia tabaci). Our findings demonstrates that type-IV glandular trichome development along with AS production and exudation are partially uncoupled at the genetic level. The MT-Get genotype represents a valuable resource for further studies involving the biochemical manipulation of type-IV trichome content through either genetic introgression or transgenic approaches. Significance StatementThis work identified loci in the tomato genome that control the heterochronic development of type-IV glandular trichomes and uncoupled the genetic control of this type of trichome ontogeny from acylsugar biosynthesis and accumulation, revealing a higher than anticipated genetic complexity of acylsugar-based insect resistance. The findings reported herein will contribute to further dissect the genetics of trichome development in tomato as well as to introgress broad and durable insect resistance in tomato and other Solanaceae.

plant biology↗

Oomycete small RNAs invade the plant RNA-induced silencing complex for virulence

Fungal small RNAs (sRNAs) hijack the plant RNA silencing pathway to manipulate host gene expression, named cross-kingdom RNA interference (ckRNAi). It is currently unknown how conserved and significant ckRNAi is for microbial virulence. Here, we found for the first time that sRNAs of a pathogen representing the oomycete kingdom invade the host plants Argonaute (AGO)/RNA-induced silencing complex. To demonstrate the functionality of the plant-invading oomycete Hyaloperonospora arabidopsidis sRNAs (HpasRNAs), we designed a novel CRISPR endoribonuclease Csy4/GUS repressor reporter to visualize in situ pathogen-induced target suppression in Arabidopsis thaliana host plant. By using 5 RACE-PCR we demonstrated HpasRNAs-directed cleavage of plant mRNAs. The significant role of HpasRNAs together with AtAGO1 in virulence was demonstrated by plant atago1 mutants and by transgenic Arabidopsis expressing a target mimic to block HpasRNAs, that both exhibited enhanced resistance. Individual HpasRNA plant targets contributed to host immunity, as Arabidopsis gene knockout or HpasRNA-resistant gene versions exhibited quantitative enhanced or reduced susceptibility, respectively. Together with previous reports, we found that ckRNAi is conserved among oomycete and fungal pathogens.

microbiology↗