Rhizobacterium-derived diacetyl modulates plant immunity in a phosphate-dependent manner
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ABSTRACT: Plants establish mutualistic associations with beneficial microbes while deploying the immune system to defend against pathogenic ones. Little is known about the interplay between mutualism and immunity and the mediator molecules enabling such crosstalk. Here we show that plants respond differentially to a volatile bacterial compound through integral modulation of the immune system and the phosphate-starvation response (PSR) system, resulting in either mutualism or immunity. We found that exposure of Arabidopsis thaliana to a known plant growth-promoting rhizobacterium can unexpectedly have either beneficial or deleterious effects to plants. The beneficial-to-deleterious transition is dependent on availability of phosphate to the plants and is mediated by diacetyl, a bacterial volatile compound. Under phosphate-sufficient conditions, diacetyl partially suppresses plant production of reactive oxygen species (ROS) and enhances symbiont colonization without compromising disease resistance. Under phosphate-deficient conditions, diacetyl enhances phytohormone-mediated immunity and consequently causes plant hypersensitivity to phosphate deficiency. Therefore, diacetyl affects the type of relation between plant hosts and certain rhizobacteria in a way that depends on the plant's phosphate-starvation response system and phytohormone-mediated immunity.
Project description:Plants establish mutualistic associations with beneficial microbes while deploying the immune system to defend against pathogenic ones. Little is known about the interplay between mutualism and immunity and the mediator molecules enabling such crosstalk. Here, we show that plants respond differentially to a volatile bacterial compound through integral modulation of the immune system and the phosphate-starvation response (PSR) system, resulting in either mutualism or immunity. We found that exposure of Arabidopsis thaliana to a known plant growth-promoting rhizobacterium can unexpectedly have either beneficial or deleterious effects to plants. The beneficial-to-deleterious transition is dependent on availability of phosphate to the plants and is mediated by diacetyl, a bacterial volatile compound. Under phosphate-sufficient conditions, diacetyl partially suppresses plant production of reactive oxygen species (ROS) and enhances symbiont colonization without compromising disease resistance. Under phosphate-deficient conditions, diacetyl enhances phytohormone-mediated immunity and consequently causes plant hyper-sensitivity to phosphate deficiency. Therefore, diacetyl affects the type of relation between plant hosts and certain rhizobacteria in a way that depends on the plant's phosphate-starvation response system and phytohormone-mediated immunity.
Project description:Plants establish mutualistic association with beneficial microbes while deploy the immune system to defend against pathogens. Little is known about the interplay between mutualism and immunity and about the mediator molecules. Here we show that plants respond differently to a bacterial volatile compound through integral modulation of the immune system and the phosphate starvation response (PSR) system, resulting in either mutualism or immunity. We found that the same exposure of a recognized plant growth-promoting rhizobacterium unexpectedly causes either beneficial or deleterious effects to plants. The beneficial-to-deleterious transition is dependent on plant nutrition of phosphorus (P) and is mediated by diacetyl (DA), a bacterial volatile compound. In P-sufficient plants, DA partially suppresses plant production of reactive oxygen species (ROS) and enhances symbiont colonization without compromising disease resistance. In P-deficient plants, DA elevates phytohormone-mediated immunity and consequently causes plant hypersensitivity to P deficiency. Therefore, DA affects the types of relation between plants and certain rhizobacteria in a way that depends on plant PSR system and phytohormone-mediated immunity.
Project description:Sphingosine 1-phosphate (S1P) is a bioactive signalling sphingolipid that is increased in diseases such as obesity and diabetes. S1P can modulate platelet function, however the direction of effect and S1P receptors (S1PRs) involved are controversial. Here we describe the role of S1P in regulating human platelet function and identify the receptor subtypes responsible for S1P priming. Human platelets were treated with protease-activated receptor 1 (PAR-1)-activating peptide in the presence or absence of S1P, S1PR agonists or antagonists, and sphingosine kinases inhibitors. S1P alone did not induce platelet aggregation but at low concentrations S1P enhanced PAR1-mediated platelet responses, whereas PAR1 responses were inhibited by high concentrations of S1P. This biphasic effect was mimicked by pan-S1PR agonists. Specific agonists revealed that S1PR1 receptor activation has a positive priming effect, S1PR2 and S1PR3 have no effect on platelet function, whereas S1PR4 and S1PR5 receptor activation have an inhibitory effect on PAR-1 mediated platelet function. Although platelets express both sphingosine kinase 1/2, enzymes which phosphorylate sphingosine to produce S1P, only dual and SphK2 inhibition reduced platelet function. These results support a role for SphK2-mediated S1P generation in concentration-dependent positive and negative priming of platelet function, through S1PR1 and S1PR4/5 receptors, respectively.
Project description:Lipocalin 2 (LCN2) is a secreted glycoprotein with roles in multiple biological processes. It contributes to host defense by interference with bacterial iron uptake and exerts immunomodulatory functions in various diseases. Here, we aimed to characterize the function of LCN2 in lung macrophages and dendritic cells (DCs) using Lcn2-/- mice. Transcriptome analysis revealed strong LCN2-related effects in CD103+ DCs during homeostasis, with differential regulation of antigen processing and presentation and antiviral immunity pathways. We next validated the relevance of LCN2 in a mouse model of influenza infection, wherein LCN2 protected from excessive weight loss and improved survival. LCN2-deficiency was associated with enlarged mediastinal lymph nodes and increased lung T cell numbers, indicating a dysregulated immune response to influenza infection. Depletion of CD8+ T cells equalized weight loss between WT and Lcn2-/- mice, proving that LCN2 protects from excessive disease morbidity by dampening CD8+ T cell responses. In vivo T cell chimerism and in vitro T cell proliferation assays indicated that improved antigen processing by CD103+ DCs, rather than T cell intrinsic effects of LCN2, contribute to the exacerbated T cell response. Considering the antibacterial potential of LCN2 and that commensal microbes can modulate antiviral immune responses, we speculated that LCN2 might cause the observed influenza phenotype via the microbiome. Comparing the lung and gut microbiome of WT and Lcn2-/- mice by 16S rRNA gene sequencing, we observed profound effects of LCN2 on gut microbial composition. Interestingly, antibiotic treatment or co-housing of WT and Lcn2-/- mice prior to influenza infection equalized lung CD8+ T cell counts, suggesting that the LCN2-related effects are mediated by the microbiome. In summary, our results highlight a novel regulatory function of LCN2 in the modulation of antiviral immunity.
Project description:All living organisms require a variety of essential elements for their basic biological functions. While the homeostasis of nutrients is highly intertwined, the molecular and genetic mechanisms of these dependencies remain poorly understood. Here, we report a discovery of a molecular pathway that controls phosphate (Pi) accumulation in plants under Zn deficiency. Using genome-wide association studies, we first identified allelic variation of the Lyso-PhosphatidylCholine (PC) AcylTransferase 1 (LPCAT1) gene as the key determinant of shoot Pi accumulation under Zn deficiency. We then show that regulatory variation at the LPCAT1 locus contributes significantly to this natural variation and we further demonstrate that the regulation of LPCAT1 expression involves bZIP23 TF, for which we identified a new binding site sequence. Finally, we show that in Zn deficient conditions loss of function of LPCAT1 increases the phospholipid Lyso-PhosphatidylCholine/PhosphatidylCholine ratio, the expression of the Pi transporter PHT1;1, and that this leads to shoot Pi accumulation.
Project description:Inorganic phosphate (Pi) has been recognized as an important signaling molecule that modulates chondrocyte maturation and cartilage mineralization. However, conclusive experimental evidence for its involvement in early chondrogenesis is still lacking. Here, using high-density monolayer (2D) and pellet (3D) culture models of chondrogenic ATDC5 cells, we demonstrate that the cell response to Pi does not correlate with the Pi concentration in the culture medium but is better predicted by the availability of Pi on a per cell basis (Pi abundance). Both culture models were treated with ITS+, 10mM β-glycerophosphate (βGP), or ITS+/10mM βGP, which resulted in three levels of Pi abundance in cultures: basal (Pi/DNA <10ng/µg), moderate (Pi/DNA=25.3 - 32.3ng/µg), and high abundance (Pi/DNA >60ng/µg). In chondrogenic medium alone, the abundance levels were at the basal level in 2D culture and moderate in 3D cultures. The addition of 10mM βGP resulted in moderate abundance in 2D and high abundance in 3D cultures. Moderate Pi abundance enhanced early chondrogenesis and production of aggrecan and type II collagen whereas high Pi abundance inhibited chondrogenic differentiation and induced rapid mineralization. Inhibition of sodium phosphate transporters reduced phosphate-induced expression of chondrogenic markers. When 3D ITS+/βGP cultures were treated with levamisole to reduce ALP activity, Pi abundance was decreased to moderate levels, which resulted in significant upregulation of chondrogenic markers, similar to the response in 2D cultures. Delay of phosphate delivery until after early chondrogenesis occurs (7 days) no longer enhanced chondrogenesis, but instead accelerated hypertrophy and mineralization. Together, our data highlights the dependence of chondroprogenitor cell response to Pi on its availability to individual cells and the chondrogenic maturation stage of these cells and suggest that appropriate temporal delivery of phosphate to ATDC5 cells in 3D cultures represents a rapid model for mechanistic studies into the effects of exogenous cues on chondrogenic differentiation, chondrocyte maturation, and matrix mineralization.
Project description:Chemosensory communication is ubiquitous in human social interaction. Androstadienone is a potential candidate human sex pheromone that is associated with social dominance and competition. The aim of the present study was to investigate the effects of androstadienone on aggression. We specifically distinguished two types of aggression, namely proactive and reactive aggression. Two hundred and six male and female participants received either androstadienone or a control carrier in a double-blind, placebo-controlled, between-participants design. Participants performed two aggression tasks, one on reactive aggression and the other on proactive aggression, while they were exposed to the olfactory stimuli. The results revealed that for men, smelling androstadienone reduced both reactive and proactive aggression, whereas it increased reactive aggression in women. These effects were present despite the olfactory stimuli not being explicitly discriminable. These findings provide direct evidence that androstadienone modulates human aggression in a sex-dependent manner.
Project description:It has been shown that neurons alter the expression of astrocytic metabolic enzymes by secretion of until now unknown molecule(s) into extracellular fluid. Here, we present evidence that neuron-derived transthyretin (TTR) stimulates expression of glycolytic enzymes in astrocytes which is reflected by an increased synthesis of ATP. The action of TTR is restricted to regulatory enzymes of glycolysis: phosphofructokinase P (PFKP) and pyruvate kinase M1/M2 isoforms (PKM1/2). The regulation of PFK and PKM expression by TTR is presumably specific for brain tissue and is independent of the role of TTR as a carrier protein for thyroxine and retinol. TTR induced expression of PKM and PFK is mediated by the cAMP/PKA-dependent pathway and is antagonized by the PI3K/Akt pathway. Our results provide the first experimental evidence for action of TTR as a neuron-derived energy metabolism activator in astrocytes and describe the mechanisms of its action. The data presented here suggest that TTR is involved in a mechanism in which neurons stimulate degradation of glycogen-derived glucosyl units without significant modulation of glucose uptake by glial cells.
Project description:Lymph nodes are highly specialized immune organs that orchestrate the adaptive immune response. In the lymph nodes, naïve B and T lymphocytes encounter cognate antigens, sparking their activation and response to foreign substances. Lymph nodes grow in response to an immune challenge, at least in part to accommodate increased numbers of infiltrating and proliferating B and T lymphocytes. This behavior is supported by a robust three-dimensional network of extracellular matrix (ECM) fibers and fibroblastic reticular cells (FRCs). ECM fibers and FRCs work synergistically to alternate stretching and contractile forces between them allowing the lymph node to maintain structural integrity during rapid tissue reconstruction. These changes ultimately alter the material properties of the lymph node, which can impact cell migration, proliferation, and differentiation. Recent work has investigated the physiological implications of the changing lymph node microenvironment; however, the biophysical properties of the lymph nodes during these changes remain largely unexplored. Here, we use multiple particle tracking microrheology (MPT), a minimally invasive nanoparticle-based technique to investigate the biophysical properties (elastic/loss moduli, microviscosity, pore size) of lymph nodes post inflammatory stimulus. Our results highlight mechanical changes both during the initial phases of the acute inflammatory response and upon resolution of inflammation, a topic that is relatively understudied. We show that B and T cell rich areas restructure independently, with T cell zones remodeling significantly and exhibiting nearly a 3-fold higher elastic modulus. Additionally, for the first time, we show that biological sex modulates lymph node biomechanics in acute inflammation: Lymph nodes from female mice showed a ~20-fold increase in elastic and loss moduli at peak inflammation, while lymph nodes from male mice had a ~5-fold decrease in both moduli. Additionally, lymph nodes from female mice appeared to permanently remodel during the resolution of acute inflammation resulting in the maintenance of an overall higher elastic and loss modulus, while lymph nodes from male mice returned to the biomechanics of untreated lymph nodes. We also found that at least some of the changes in biomechanical properties were correlated with changes in ECM materials in the lymph nodes, suggesting a structure-function relationship. Overall, our studies provide key insights into how biomechanical properties in lymph nodes are altered during inflammation, a previously unstudied area, and lay the foundation for structure-function relationships involved in immune response. Additionally, we demonstrate a robust technique for the analysis of the lymph node interstitial tissue properties and how they vary with inflammatory stimuli.