Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition

Immune evasion is a hallmark of persistent echinococcal infection, comprising modulation of innate immune cells and antigen-specific T cell responses. However, recognition of Echinococcus granulosus by dendritic cells (DCs) is a key determinant of the host's response to this parasite. Given that mTOR signaling pathway has been described as a regulator linking metabolism and immune function in DCs, we reported for the first time in these cells, global translation levels, antigen uptake, phenotype, cytokine transcriptional levels, and splenocyte priming activity upon recognition of the hydatid fluid (HF) and the highly glycosylated laminar layer (LL). We found that LL induced a slight up-regulation of CD86 and MHC II in DCs and also stimulated the production of IL-6 and TNF-α. By contrast, HF did not increase the expression of any co-stimulatory molecules, but also down-modulated CD40 and stimulated the expression of the anti-inflammatory cytokine IL-10. Both parasitic antigens promoted protein synthesis through mTOR activation. The use of rapamycin decreased the expression of the cytokines tested, empowered the down-modulation of CD40 and also reduced splenocyte proliferation. Finally, we showed that E. granulosus antigens increase the amounts of LC3-positive structures in DCs which play critical roles in the presentation of these antigens to T cells.

ELICE16INDURES ®: a plant immune-priming activator targeting jasmonate metabolism via TIFY and RHOMBOID proteins in Hordeum vulgare

Priming activity of plant-based allelochemicals is advanced research nowadays meaning a high potential in sustainable agriculture. The ELICE16INDURES® (RIMPH LTD, Hungary) plant conditioner of CO2 botanical extracts is rich in plant-active ingredients such as phenolic compounds, alkaloids, and flavonoids formulated in small multilamellar liposomes. This product was investigated in autumn barley (Hordeum vulgare). Field experiments of ELICE16INDURES showed augmented NDVI values interconnected with higher photosynthetic activity and yield increase. Background of the better vitality of plants was investigated by whole genomic gene expression profiling and showed an enhanced response to wounding, jasmonic acid, oxidative detoxification, and chloroplast activity. Among top 50 differentially expressed genes the TIFY domain protein TIFY11B and RHOMBOID-like protein 2 related to JA signaling were up-regulated in field-collected samples. Phytotron experiments of barley were set up to validate and evaluate the transcriptomic effect of ELICE16INDURES. Well-studied priming active agents such as salicylic acid and beta-aminobutyric acid were compared with ELICE16INDURES and confirmed as priming inducer material with positive regulation of TIFY11B, TIFY3B, TIFY9, TIF10A, and RHOMBOID like protein 2 by using NGS GEx and RT-qPCR methods.

Single and Combined Salinity and Heat Stresses Impact Yield and Dead Pericarp Priming Activity

In the face of climate change and the predicted increase in the frequency and severity of abiotic stresses (e.g., hot spell, salinity), we sought to investigate the effect of salinity (S), short episodes of high temperature (HS) and combination of salinity and high temperature (SHS), at the reproductive phase, on yield with a special focus on the properties of dead pericarps of Brassica juncea. Three interval exposures to HS resulted in massive seed abortion, and seeds from salt-treated plants germinated poorly. Germination rate and final germination of B. juncea seeds were slightly reduced in the presence of salt and SHS pericarp extracts. All pericarp extracts completely inhibited seed germination of tomato and Arabidopsis, but removal of pericarp extracts almost fully restored seed germination. Heat and salinity profoundly affected the accumulation of phytohormones in dead pericarps. Combined stresses highly reduced IAA and ABA levels compared with salt, and enhanced the accumulation of GA1, but abolished the positive effect of salt on the accumulation of GA4, JA and SA. Interestingly, pericarp extracts displayed priming activity and significantly affected seedling performance in a manner dependent on the species and on the origin of the pericarp. While control pericarps improved and reduced the seedlings’ performance of autologous and heterologous species, respectively, pericarps from salt-treated plants were harmless or improved heterologous seedling performance. Thus, the strategy employed by the germinating seed for securing resources is set up, at least partly, by the mother plant in conjunction with the maternal environment whose components are stored in the dead maternal organs enclosing the embryo.

The AIM2 and NLRP3 inflammasomes trigger IL-1–mediated antitumor effects during radiation

The inflammasome promotes inflammation-associated diseases, including cancer, and contributes to the radiation-induced tissue damage. However, the role of inflammasome in radiation-induced antitumor effects is unclear. We observed that tumors transplanted in Casp1−/− mice were resistant to radiation treatment compared with tumors in wild-type (WT) mice. To map out which molecule in the inflammasome pathway contributed to this resistant, we investigated the antitumor effect of radiation in several inflammasome-deficient mice. Tumors grown in either Aim2−/− or Nlrp3−/− mice remained sensitive to radiation, like WT mice, whereas Aim2−/−Nlrp3−/− mice showed radioresistance. Mechanistically, extracellular vesicles (EVs) and EV-free supernatant derived from irradiated tumors activated both Aim2 and Nlrp3 inflammasomes in macrophages, leading to the production of interleukin-1β (IL-1β). IL-1β treatment helped overcome the radioresistance of tumors growing in Casp1−/− and Aim2−/−Nlrp3−/− mice. IL-1 signaling in dendritic cells (DCs) promoted radiation-induced antitumor immunity by enhancing the cross-priming activity of DCs. Overall, we demonstrated that radiation-induced activation of the AIM2 and NLRP3 inflammasomes coordinate to induce some of the antitumor effects of radiation by triggering IL-1 signaling in DCs, leading to their activation and cross-priming.

Phenolic acid-degrading Paraburkholderia prime decomposition in forest soil

Plant-derived phenolic acids are catabolized by soil microorganisms whose activity may enhance the decomposition of soil organic carbon (SOC). We characterized whether phenolic acid-degrading bacteria enhance SOC mineralization in forest soils when primed with 13C-labeled p-hydroxybenzoic acid (pHB). We further tested whether pHB-induced priming could explain differences in SOC content among mono-specific tree plantations in a 70-year-old common garden experiment. pHB addition primed significant losses of SOC (3–13 µmols C g−1 dry wt soil over 7 days) compared to glucose, which reduced mineralization (-3 to -8 µmols C g−1 dry wt soil over 7 days). The principal degraders of pHB were Paraburkholderia and Caballeronia in all plantations regardless of tree species or soil type, with one predominant phylotype (RP11ASV) enriched 23-fold following peak pHB respiration. We isolated and confirmed the phenolic degrading activity of a strain matching this phylotype (RP11T), which encoded numerous oxidative enzymes, including secretion signal-bearing laccase, Dyp-type peroxidase and aryl-alcohol oxidase. Increased relative abundance of RP11ASV corresponded with higher pHB respiration and expression of pHB monooxygenase (pobA), which was inversely proportional to SOC content among plantations. pobA expression proved a responsive measure of priming activity. We found that stimulating phenolic-acid degrading bacteria can prime decomposition and that this activity, corresponding with differences in tree species, is a potential mechanism in SOC cycling in forests. Overall, this study highlights the ecology and function of Paraburkholderia whose associations with plant roots and capacity to degrade phenolics suggest a role for specialized bacteria in the priming effect.

Strand-specific detection of overlapping transcripts via purification involving denaturation of biotinylated cDNA

Reverse transcription-PCR (RT-PCR) is the most widely employed technique for gene expression analysis owing to its high sensitivity, easy reproducibility and fast output. It has been conceived that priming RT reactions with gene-specific primers generates cDNA only from the specific RNA. However, several reports have revealed that cDNA is synthesized even without addition of exogenous primers in RT reactions. Owing to such self-priming activity, the signals from specific strands cannot be accurately detected and can confound the expression analysis, especially in context of overlapping bidirectional transcripts. Here, we demonstrate that purification of biotin-tagged cDNA in conjunction with alkaline denaturation can obviate the problem of background priming and enable accurate strand-specific detection of overlapping transcripts.

Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition

1.AbstractImmune evasion is a hallmark of persistent echinococcal infection, comprising modulation of innate immune cells and antigen-specific T cell responses. However, recognition of Echinococcus granulosus by dendritic cells (DCs) is a key determinant of the host’s response to this parasite. Given that mTOR signaling pathway has been described as a regulator linking metabolism and immune function in DCs, we reported for the first time in these cells, global translation levels, antigen uptake, phenotype, cytokine transcriptional levels, and splenocyte priming activity upon recognition of the hydatid fluid (HF) and the highly glycosylated laminar layer (LL). We found that LL induced a slight up-regulation of CD86 and MHC II in DCs and also stimulated the production of IL-6 and TNF-α. By contrast, HF did not increase the expression of any co-stimulatory molecules, but also down-modulated CD40 and stimulated the expression of the anti-inflammatory cytokine IL-10. Both parasitic antigens promoted protein synthesis through mTOR activation. The use of rapamycin decreased the expression of the cytokines tested, empowered the down-modulation of CD40 and also reduced splenocyte proliferation. Finally, we showed that E. granulosus antigens increase the amounts of LC3-positive structures in DCs which play critical roles in the presentation of these antigens to T cells.

The effect of different priming activities performed 24 hours prior to competition

The purpose of this study was to examine if performing a lower body resistance training priming activity effects athletic performance completed 24 hours later. University level field hockey players (N = 10) completed 1 control (CON) and 2 experimental trials on separate days. A randomised, counter-balanced experimental design with cross-over was used across three conditions. The CON trial consisted of complete abstention from physical activity. For the ‘strength’ (STR) experimental trial participants performed a parallel back squat exercise for 5 sets of 2 repetitions with 90% 1RM; while for the ‘hypertrophy’ (HYP) experimental approach was 3 sets of 10 repetitions with 75% 1RM. Subjects attended a testing session 24 hours after each trial, consisting of CMJ, SJ, 22-cm DJ, 38-cm DJ and 40 m sprint. The 5 m sprint performance was significantly better (p < 0.05) for CON group when compared to the HYP group. No other significant differences were highlighted between trials. The results indicate that performing resistance training in-line with STR and HYP the day before competition does not improve athletes’ performance. The results also suggest how a lower body STR priming activity can be implemented the day before competition without negatively impact subsequent performance. For the strength and conditioning coach, this may be a useful window to train athletes during the ‘in-season’ schedule.

The Pattern of Acetylation Defines the Priming Activity of Chitosan Tetramers

The biological activity of chitosans depends on their degree of polymerization (DP) and degree of acetylation (DA). However, information could also be carried by the pattern of acetylation (PA): the sequence of <i>β</i>-1,4-linked glucosamine (deacetylated/D) and <i>N</i>-acetylglucosamine (acetylated/A) units. To address this hypothesis, we prepared partially-acetylated chitosan oligosaccharides from a chitosan polymer (DA=35%, DP_w=905) using recombinant chitosan hydrolases with distinct substrate and cleavage specificities. The mixtures were separated into fractions DP4–DP12, which were tested for elicitor and priming activities in rice cells. We confirmed that both activities were influenced by DP, <a>but also observed apparent DA-dependent priming activity, with the ADDD+DADD fraction proving remarkably effective</a>. We then compared all four mono-acetylated tetramers prepared using different chitin deacetylases and observed significant differences in priming activity. This demonstrates for the first time that PA influences the biological activity of chitosans, which can now be recognized as <i>bona fide</i> information-carrying molecules