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Climate-induced changes contribute to the thawing of ice-rich permafrost in the Arctic, which leads to the release of large amounts of organic carbon into the atmosphere in the form of greenhouse gases, mainly carbon dioxide and methane. Ground ice constitutes a considerable volume of the cryogenically sequestered labile dissolved organic carbon (DOC) subjected to fast mineralization upon thawing. In this work, we collected a unique geochemical database of the ground and glacier ice comprising the samples from various geographic locations in the Russian Arctic characterized by a variety of key parameters, including ion composition, carbon-bearing gases (methane and carbon dioxide), bulk biogeochemical indicators, and fluorescent dissolved organic matter (DOM) fractions. Our results show that interaction with solid material—such as sediments, detritus, and vegetation—is likely the overriding process in enrichment of the ground ice in all the dissolved compounds. Terrigenous humic-like dissolved organic matter was predominant in all the analyzed ice samples except for glacier ice from Bolshevik Island (the Severnaya Zemlya archipelago) and pure (with low sediment content) tabular ground ice from western Yamal. The labile protein-like DOM showed no correlation to humic components and was probably linked to microbial abundance in the ground ice. The sum of the fluorophores deconvoluted by PARAFAC strongly correlates to DOC, which proves the potential of using this approach for differentiation of bulk DOC into fractions with various origins and biogeochemical behaviors. The pure tabular ground ice samples exhibit the highest rate of fresh easily degradable DOM in the bulk DOC, which may be responsible for the amplification of permafrost organic matter decomposition upon thawing.

The proposed advantages of intra-arterial chemotherapy (IAC) are based on the premises of local dose escalation to the tumor and reduced availability of systemic drugs. There is a lack of objective pharmacokinetic data to confirm the advantage of IAC in dogs with naturally occurring urogenital tumors. The objective of this study was to determine if IAC administration in urogenital tumors would result in decreased systemic drug exposure when compared to intravenous routes. Twenty-two dogs with naturally occurring urogenital tumors were enrolled in this prospective case-controlled study. Mitoxantrone, doxorubicin, or carboplatin were administered by IAC and intravenous routes [intravenous awake (intravenous chemotherapy - IVC) and under general anesthesia (IVGAC)] 3 weeks apart. Serum assays were used to determine the extent of systemic drug exposure. Dose-normalized peak systemic serum concentration (Cmax) and area under the serum drug concentration-time curve (AUC) were used to quantify systemic exposure. A total of 26 mitoxantrone treatments were administered to 10 dogs. While there was no significant difference in Cmax, the AUC was significantly lower after IAC compared with IVGAC. Ten doxorubicin treatments were administered to 5 dogs. There were no significant differences in Cmax or AUC. A total of 14 carboplatin treatments were administered to 7 dogs. The Cmax was significantly lower for IAC compared to IVC, while the AUC values were equivocal. This study demonstrates certain lower serum values may be achieved after IAC delivery of carboplatin and mitoxantrone. These chemotherapy agents may have a preferred pharmacological profile for regional chemotherapy delivery in dogs with urogenital tumors.

Botrytis cinerea is the causative agent of gray mold disease, and infects more than 1400 plant species, including important crop plants. In tomato, B. cinerea causes severe damage in greenhouses and post-harvest storage and transport. Plant viruses of the Tobamovirus genus cause significant damage to various crop species. In recent years, the tobamovirus tomato brown rugose fruit virus (ToBRFV) has significantly affected the global tomato industry. Most studies of plant-microbe interactions focus on the interaction between the plant host and a single pathogen, however, in agricultural or natural environments, plants are routinely exposed to multiple pathogens. Here, we examined how preceding tobamovirus infection affects the response of tomato to subsequent infection by B. cinerea. We found that infection with the tobamoviruses tomato mosaic virus (ToMV) or ToBRFV resulted in increased susceptibility to B. cinerea. Analysis of the immune response of tobamovirus-infected plants revealed hyper-accumulation of endogenous salicylic acid (SA), upregulation of SA-responsive transcripts, and activation of SA-mediated immunity. Deficiency in SA biosynthesis decreased tobamovirus-mediated susceptibility to B. cinerea, while exogenous application of SA enhanced B. cinerea symptoms. These results suggest that tobamovirus-mediated accumulation of SA increases the plants’ susceptibility to B. cinerea, and provide evidence for a new risk caused by tobamovirus infection in agriculture.

Background: Transforming growth factor (TGF)-ß1 is a pleiotropic cytokine that can promote tumor growth and suppress antitumor immune responses. Latent TGF-ß1 associates with glycoprotein-A repetition predominant (GARP) on the surface of regulatory T cells prior to its activation and release. Livmoniplimab is a monoclonal antibody (mAb) that binds the GARP:TGF-ß1 complex to inhibit activation and release of TGF-ß1. It is in clinical development in combination with budigalimab, an anti-programmed cell death protein 1 Fc-modified mAb. The first-in-human, phase 1, dose-escalation results are presented herein (ClinicalTrials.gov : NCT03821935). Methods: The dose-escalation phase enrolled adult patients with advanced solid tumors. Patients received escalating doses of livmoniplimab ranging from 3mg to 1500mg, once every 2 weeks (Q2W), as monotherapy or in combination with a 500mg fixed dose of budigalimab Q4W. The primary objective of the dose escalation was to determine the recommended phase 2 dose. Secondary objectives were to assess safety and pharmacokinetics (PK), and exploratory objectives included evaluating preliminary efficacy. Results: Fifty-seven patients enrolled in the dose escalation: 23 in monotherapy cohorts and 34 in combination therapy cohorts. Dose-limiting toxicities were limited, no maximum tolerated dose was reached, and the maximum administered dose of 1500mg was selected for dose expansion. The most common adverse events reported in monotherapy-treated patients were fatigue, anemia, and nausea, and those in combination therapy-treated patients were pruritus, fatigue, nausea, and anemia. Livmoniplimab exhibited dose-proportional PK, and peripheral blood biomarker data demonstrated saturation of the GARP:TGF-ß1 complex on platelets at livmoniplimab doses within the linear PK range. No objective tumor responses were observed in the monotherapy dose escalation. However, the objective response rate was 15% in the combination dose escalation, with a median response duration of 8.4 months. Conclusion: Livmoniplimab was well-tolerated as monotherapy and in combination with budigalimab in the dose-escalation phase. Encouraging preliminary efficacy was demonstrated in the combination dose escalation in heavily pretreated patients, supporting further development of this novel drug combination in patients with advanced solid tumors. [ABSTRACT FROM AUTHOR]

During our search for aphid-pathogenic viruses, a comovirus was isolated from wild asymptomatic Brassica hirta (white mustard) plants harboring a dense population of Brevicoryne brassicae aphids. The transmission-electron-microscopy visualization of purified virions revealed icosahedral particles. The virus was mechanically transmitted to plants belonging to Brassicaceae, Solanaceae, Amaranthaceae, and Fabaceae families, showing unique ringspot symptoms only on B. rapa var. perviridis plants. The complete viral genome, comprised of two RNA segments, was sequenced. RNA1 and RNA2 contained 5921 and 3457 nucleotides, respectively, excluding the 3′ terminal poly-adenylated tails. RNA1 and RNA2 each had one open-reading frame encoding a polyprotein of 1850 and 1050 amino acids, respectively. The deduced amino acids at the Pro-Pol region, delineated between a conserved CG motif of 3C-like proteinase and a GDD motif of RNA-dependent RNA polymerase, shared a 96.5% and 90% identity with the newly identified Apis mellifera-associated comovirus and Arabidopsis latent virus 1 (ArLV1), respectively. Because ArLV1 was identified early in 2018, the B. hirta comovirus was designated as ArLV1-IL-Bh. A high-throughput-sequencing-analyses of the extracted RNA from managed honeybees and three abundant wild bee genera, mining bees, long-horned bees, and masked bees, sampled while co-foraging in a Mediterranean ecosystem, allowed the assembly of ArLV1-IL-Bh, suggesting pollinators’ involvement in comovirus spread in weeds.

Plant recognition and defence against pathogens employs a two-tiered perception system. Surface-localized pattern recognition receptors (PRRs) act to recognize microbial features, whereas intracellular nucleotide-binding leucine-rich repeat receptors (NLRs) directly or indirectly recognize pathogen effectors inside host cells. Employing the tomato PRR LeEIX2/EIX model system, we explored the molecular mechanism of signalling pathways. We identified an NLR that can associate with LeEIX2, termed SlNRC4a (NB-LRR required for hypersensitive response-associated cell death-4). Co-immunoprecipitation demonstrates that SlNRC4a is able to associate with different PRRs. Physiological assays with specific elicitors revealed that SlNRC4a generally alters PRR-mediated responses. SlNRC4a overexpression enhances defence responses, whereas silencing SlNRC4 reduces plant immunity. Moreover, the coiled-coil domain of SlNRC4a is able to associate with LeEIX2 and is sufficient to enhance responses upon EIX perception. On the basis of these findings, we propose that SlNRC4a acts as a noncanonical positive regulator of immunity mediated by diverse PRRs. Thus, SlNRC4a could link both intracellular and extracellular immune perceptions.

RNA-dependent RNA polymerase 1 (RDR1) plays a crucial role in plant defence against viruses. In this study, it was observed that cucumber, Cucumis sativus, uniquely encodes a small gene family of four RDR1 genes. The cucumber RDR1 genes (CsRDR1a, CsRDR1b and duplicated CsRDR1c1/c2) shared 55%-60% homology in their encoded amino acid sequences. In healthy cucumber plants, RDR1a and RDR1b transcripts were expressed at higher levels than transcripts of RDR1c1/c2, which were barely detectable. The expression of all four CsRDR1 genes was induced by virus infection, after which the expression level of CsRDR1b increased 10-20-fold in several virus-resistant cucumber cultivars and in a broad virus-resistant transgenic cucumber line expressing a high level of transgene small RNAs, all without alteration in salicylic acid (SA) levels. By comparison, CsRDR1c1/c2 genes were highly induced (25-1300-fold) in susceptible cucumber cultivars infected with RNA or DNA viruses. Inhibition of RDR1c1/c2 expression led to increased virus accumulation. Ectopic application of SA induced the expression of cucumber RDR1a, RDR1b and RDRc1/c2 genes. A constitutive high level of RDR1b gene expression independent of SA was found to be associated with broad virus resistance. These findings show that multiple RDR1 genes are involved in virus resistance in cucumber and are regulated in a coordinated fashion with different expression profiles.

Plants are constantly exposed to numerous diverse microbes and pests. They lack an adaptive immune system and rely on innate immunity to perceive and ward off potential pathogens. The plant immune system enables plants to overcome invading microorganisms, and can be defined as highly successful in this regard. Nevertheless, specialized pathogens are able to overcome structural barriers, preformed defenses, innate immunity and are a persistent threat to crop and food supplies worldwide. The rapidly growing world population results in massive demands for agricultural products and reliable crop yields. Therefore, the ability to precisely manipulate plant immunity to resist diverse diseases holds significant promise for enhancing crop production.

Abstract Studies of early stages of cucumber green mottle mosaic virus (CGMMV) disease have been recently focused on plant molecular responses. However, extreme diurnal environmental temperatures, characteristic of global climate changes, could affect plant susceptibility and disease phenotype progression. Our studies of CGMMV disease progression, under simulated extreme temperature waves, have revealed two new disease initiation phenotypes that developed gradually, preceding severe symptom manifestations of post-recovery CGMMV systemic infections. 'Early post-recovery stage' bright yellow islands (BYIs) with defined boundaries amid asymptomatic leaf blades were first emerging followed by 'late post-recovery stage' BYIs with diffused boundaries. A deduced CGMMV disease progression scheme, postulating BYI symptom occurrence time-windows, revealed BYIs in field grown cucumber plants exposed to extreme diurnal temperatures. Profiling ontology of cucumber differentially expressed genes in BYIs vs the associated dark-green surrounding tissues disclosed activation of jasmonic acid (JA) pathway in 'early post-recovery stage' BYIs. JA signaling was inactivated in 'late post-recovery stage' BYIs concomitant with increasing expressions of JA signaling inhibitors and downregulation of JA responsive phenylpropanoid pathway. Our results disclosed a new phenotypic description of CGMMV disease initiation, characteristic of cucumbers grown under extreme environmental temperature fluctuations. The BYI phenotypes could define a time-window for CGMMV disease management applications.

The Arctic zone of West Siberia (Yamal and Gydan peninsulas) is an area with continuous permafrost and tabular ground ice close to the surface, active thermodenudation, and related landforms: retrogressive thaw slumps (RTS); in Russian referred to as thermocirques (TC). The dimensions of most TCs have not been determined so far. We use Sentinel 2 imagery to measure each TC area ranging from 0.55 to 38 ha with a median of 2.5 ha. Around 95% of TCs have an area of less than 10 ha. The largest areas are gained due to the merging of several neighboring TCs. The ArcticDEM is used to determine TC edge elevation and slope angle. In general, the Median TC of the Yamal peninsula has an area of 1.8 ha, an elevation of the edge of 17.7 m, and a slope angle of 2.5°. The Median TC of the Gydan peninsula has an area of 2.6 ha, elevation of the edge of 29.4 m, and slope angle of 3°. TCs of the Gydan peninsula occupy higher positions and slightly steeper slopes compared to TCs of the Yamal peninsula. The ranges of the median and the largest TC areas are consistent with the reported RTS dimensions in North America.

Background: Transforming growth factor (TGF)-ß1 is a pleiotropic cytokine that can promote tumor growth and suppress antitumor immune responses. Latent TGF-ß1 associates with glycoprotein-A repetition predominant (GARP) on the surface of regulatory T cells prior to its activation and release. Livmoniplimab is a monoclonal antibody (mAb) that binds the GARP:TGF-ß1 complex to inhibit activation and release of TGF-ß1. It is in clinical development in combination with budigalimab, an anti-programmed cell death protein 1 Fc-modified mAb. The first-in-human, phase 1, dose-escalation results are presented herein (ClinicalTrials.gov : NCT03821935). Methods: The dose-escalation phase enrolled adult patients with advanced solid tumors. Patients received escalating doses of livmoniplimab ranging from 3mg to 1500mg, once every 2 weeks (Q2W), as monotherapy or in combination with a 500mg fixed dose of budigalimab Q4W. The primary objective of the dose escalation was to determine the recommended phase 2 dose. Secondary objectives were to assess safety and pharmacokinetics (PK), and exploratory objectives included evaluating preliminary efficacy. Results: Fifty-seven patients enrolled in the dose escalation: 23 in monotherapy cohorts and 34 in combination therapy cohorts. Dose-limiting toxicities were limited, no maximum tolerated dose was reached, and the maximum administered dose of 1500mg was selected for dose expansion. The most common adverse events reported in monotherapy-treated patients were fatigue, anemia, and nausea, and those in combination therapy-treated patients were pruritus, fatigue, nausea, and anemia. Livmoniplimab exhibited dose-proportional PK, and peripheral blood biomarker data demonstrated saturation of the GARP:TGF-ß1 complex on platelets at livmoniplimab doses within the linear PK range. No objective tumor responses were observed in the monotherapy dose escalation. However, the objective response rate was 15% in the combination dose escalation, with a median response duration of 8.4 months. Conclusion: Livmoniplimab was well-tolerated as monotherapy and in combination with budigalimab in the dose-escalation phase. Encouraging preliminary efficacy was demonstrated in the combination dose escalation in heavily pretreated patients, supporting further development of this novel drug combination in patients with advanced solid tumors. [ABSTRACT FROM AUTHOR]

Retrogressive thaw slumps (RTSs) are spectacular landforms that occur due to the thawing of ice-rich permafrost or melting of massive ground ice, often in hillslope terrain. RTSs occur in the Arctic, the subarctic, and high mountain (Qinghai–Tibet Plateau) permafrost regions and are observed to expand in size and number due to climate warming. As the observation of RTSs is receiving more and more attention due to their important role in permafrost thaw; impacts on topography; mobilization of sediment, carbon, nutrients, and contaminants; and their effects on downstream hydrology and water quality, the thematic breadth of studies increases and scientists from different scientific backgrounds and perspectives contribute to new RTS research. At this point, a wide range of terminologies originating from different scientific schools is used, and we identified the need to provide an overview of variable characteristics of RTSs to clarify terminologies and ease the understanding of the literature related to RTS processes, dynamics, and feedbacks. We review the theoretical geomorphological background of RTS formation and landform characteristics to provide an up-to-date understanding of the current views on terminology and underlying processes. The presented overview can be used not only by the international permafrost community but also by scientists working on ecological, hydrological, and biogeochemical consequences of RTS occurrence and by remote-sensing specialists developing automated methods for mapping RTS dynamics. The review will foster a better understanding of the nature and diversity of RTS phenomena and provide a useful base for experts in the field but also ease the introduction to the topic of RTSs for scientists who are new to it. [ABSTRACT FROM AUTHOR]

Background: Socioeconomic status (SES) affects outcomes following surgery for various cancers. There are currently no Australian studies that examine the role of socioeconomic disadvantage on outcomes following oesophagectomy for cancer. This study assessed whether SES was associated with short‐term perioperative morbidity, long‐term survival, and oncological outcomes following oesophagectomy across three tertiary oesophageal cancer centres in Australia. Methods: A retrospective cohort study was performed comprising all patients who underwent oesophagectomy for cancer across three Australian centres. Patients were stratified into SES groups using the Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD). Outcomes measured included perioperative complication rates, overall survival, and disease‐free survival. Results: The study cohort was 462 patients, 205 in the lower SES and 257 in the higher SES groups. The lower SES group presented with more advanced oesophageal cancer stage, a higher rate of T3 (52.6% versus 42.7%, P = 0.038) and N2 disease (19.6% versus 10.5%, P = 0.006), and had a higher rate of readmission within 30 days (11.2% versus 5.4%, P = 0.023). There was no difference in overall survival or disease‐free survival between groups. Conclusion: Lower socioeconomic status was associated with more advanced stage and increased risk of early, unplanned readmission following oesophagectomy, but was not associated with a difference in overall or disease‐free survival. [ABSTRACT FROM AUTHOR]

Background: Oesophagectomy is the mainstay of curative treatment for oesophageal cancer. The role of neoadjuvant therapy has evolved over time as evidence for its survival benefit comes to hand. Clinician reluctance to offer patients neoadjuvant therapy may be based on the perception that patients receiving treatment before surgery may be exposed to a greater risk of perioperative complications. The aim of this study was to examine short‐term outcomes in patients who undergo neoadjuvant therapy versus up‐front surgery in patients with oesophageal cancer. Methods: This was a retrospective cohort study of prospectively collated data from 2001 to 2020 of patients undergoing resection for oesophageal cancer. Patients who had neoadjuvant chemoradiotherapy, chemotherapy and up‐front surgery were compared for perioperative morbidity (via the Clavien–Dindo classification), length of stay, unplanned readmission, and 30‐ and 90‐day mortality. Logistic regression was performed to predict perioperative morbidity following surgery. Results: In total, 284 patients underwent an oesophagectomy. Most patients received neoadjuvant treatment (41% received chemoradiotherapy (117/284), 33% received chemotherapy (93/284)), and 26% of patients received up‐front surgery (74/284). Patients who received neoadjuvant chemoradiotherapy or up‐front surgery were more likely to have a complication (57%, 67/117 and 57%, 43/74) than patients who received neoadjuvant chemotherapy only (38%, 35/93, P = 0.009). The 30‐ and 90‐day mortality rates were 1.4% (n = 4) and 2.8% (n = 8), respectively, with no difference between the use of neoadjuvant therapy. Conclusion: In this series, we found that patients who received neoadjuvant treatment could undergo oesophagectomy with curative intent with acceptable postoperative morbidity and mortality. [ABSTRACT FROM AUTHOR]

ABBV-184, a novel survivin peptide-targeting T-cell receptor (TCR)/anti-CD3 bispecific protein, demonstrated preclinical T-cell activation and cytotoxicity toward HLA-A2:01-positive tumor lines. This first-in-human trial evaluated ABBV-184 monotherapy in patients with acute myeloid leukemia (AML) and non-small cell lung cancer (NSCLC). This phase 1 multicenter, open-label, dose escalation trial (NCT04272203) enrolled adult patients with relapsed/refractory AML or NSCLC with an HLA-A2:01 restricted genotype. Patients received ABBV-184 at 0.07 ug/kg initially, with 2- to 3-fold dose increases. The primary objective was determining the ABBV-184 recommended phase 2 dose. Secondary objectives included safety, tolerability, pharmacokinetics, and immunogenicity assessments. Fifteen patients enrolled in the dose escalation (8 AML and 7 NSCLC). ABBV-184 doses ranged from 0.07 mg/kg–0.7 µg/kg, with a half-life of approximately 13–29 hours. Transient cytokine increases were observed at all dose levels, and in patients with NSCLC, transient peripheral blood lymphocyte decreases were observed. The most frequently reported treatment-emergent adverse events (TEAEs) were anemia, diarrhea, and headache. Grade 1–2 infusion-related reaction (IRR) and cytokine release syndrome (CRS) TEAEs were reported. ABBV-184 was well tolerated and demonstrated preliminary evidence of CD3 engagement with transient cytokine increases and peripheral lymphocyte decreases. NCT04272203 [ABSTRACT FROM AUTHOR]

Background: Extensor carpi ulnaris (ECU) subsheath injuries are an increasingly recognized cause of ulnar-sided wrist pain in elite athletes. There is a lack of surgical outcome data in elite athletes, and unique considerations exist for these patients. Methods: We performed a retrospective review of our hand center experience of 14 elite professional or collegiate athletes who prospectively underwent radially based extensor retinacular sling ECU subsheath reconstruction by 3 hand surgery-fellowship-trained surgeons between April 2011 and April 2021. Clinical, magnetic resonance imaging (MRI), and intraoperative findings were cataloged. Subgroup analyses of elite hockey players and acute subsheath injuries were also conducted. Statistical analysis was performed via a 2-tailed paired t test. Results: Mean age at the time of surgery was 21.3 years (range, 18-34). Mean time from symptom onset to surgery was 102.1 ± 110.7 days. All 14 patients underwent preoperative MRI. Five patients (35.7%) had intrinsic ECU tendinopathy, 9 patients (64.3%) had ECU tenosynovitis, 6 patients (42.9%) had triangular fibrocartilage complex tears, and 9 patients (64.3%) had ulnocarpal synovitis. Mean postoperative pain on a Visual Analog Scale was 0.25 ± 0.43. Grip strength (P =.001), wrist flexion-extension (P =.037), and pronosupination arcs (P =.093) showed excellent recovery postoperatively. Mean time to unrestricted return to sports was 92.5 ± 21.0 days. There were no complications. Subgroup analyses found similar functional improvement and characterized injury patterns. Conclusions: Overall, our findings suggest surgical management of ECU subsheath injuries is a viable option in both acute and chronic settings in elite athletes and may be favorable compared with nonoperative management. [ABSTRACT FROM AUTHOR]

Microbiological, molecular ecological, biogeochemical, and isotope geochemical research was carried out in four lakes of the central part of the Yamal Peninsula in the area of continuous permafrost. Two of them were large (73.6 and 118.6 ha) and deep (up to 10.6 and 12.3 m) mature lakes embedded into all geomorphological levels of the peninsula, and two others were smaller (3.2 and 4.2 ha) shallow (2.3 and 1.8 m) lakes which were formed as a result of thermokarst on constitutional (segregated) ground ice. Samples were collected in August 2019. The Yamal tundra lakes were found to exhibit high phytoplankton production (340–1200 mg C m−2 d−1) during the short summer season. Allochthonous and autochthonous, particulate and dissolved organic matter was deposited onto the bottom sediments, where methane was the main product of anaerobic degradation, and its content was 33–990 µmol CH4 dm−3. The rates of hydrogenotrophic methanogenesis appeared to be higher in the sediments of deep lakes than in those of the shallow ones. In the sediments of all lakes, Methanoregula and Methanosaeta were predominant components of the archaeal methanogenic community. Methane oxidation (1.4–9.9 µmol dm−3 d−1) occurred in the upper sediment layers simultaneously with methanogenesis. Methylobacter tundripaludum (family Methylococcaceae) predominated in the methanotrophic community of the sediments and the water column. The activity of methanotrophic bacteria in deep mature lakes resulted in a decrease in the dissolved methane concentration in lake water from 0.8–4.1 to 0.4 µmol CH4 L−1 d−1, while in shallow thermokarst lakes the geochemical effect of methanotrophs was much less pronounced. Thus, only small, shallow Yamal lakes may contribute significantly to the overall diffusive methane emissions from the water surface during the warm summer season. The water column of large, deep lakes on Yamal acts, however, as a microbial filter preventing methane emission into the atmosphere. It can be assumed that climate warming will lead to an increase in the total area of thermokarst lakes, which will enhance the effect of methane release into the atmosphere.

ABSTRACT Beneficial interaction of members of the fungal genus Trichoderma with plant roots primes the plant immune system, promoting systemic resistance to pathogen infection. Some strains of Trichoderma virens produce gliotoxin, a fungal epidithiodioxopiperazine (ETP)-type secondary metabolite that is toxic to animal cells. It induces apoptosis, prevents NF-κB activation via the inhibition of the proteasome, and has immunosuppressive properties. Gliotoxin is known to be involved in the antagonism of rhizosphere microorganisms. To investigate whether this metabolite has a role in the interaction of Trichoderma with plant roots, we compared gliotoxin-producing and nonproducing T. virens strains. Both colonize the root surface and outer layers, but they have differential effects on root growth and architecture. The responses of tomato plants to a pathogen challenge were followed at several levels: lesion development, levels of ethylene, and reactive oxygen species. The transcriptomic signature of the shoot tissue in response to root interaction with producing and nonproducing T. virens strains was monitored. Gliotoxin producers provided stronger protection against foliar pathogens, compared to nonproducing strains. This was reflected in the transcriptomic signature, which showed the induction of defense-related genes. Two markers of plant defense response, PR1 and Pti-5, were differentially induced in response to pure gliotoxin. Gliotoxin thus acts as a microbial signal, which the plant immune system recognizes, directly or indirectly, to promote a defense response. IMPORTANCE A single fungal metabolite induces far-reaching transcriptomic reprogramming in the plant, priming immune responses and defense, in contrast to its immunosuppressive effect on animal cells. While the negative effects of gliotoxin-producing Trichoderma strains on growth may be observed only under a particular set of laboratory conditions, gliotoxin-linked molecular patterns, including the potential for limited cell death, could strongly prime plant defense, even in mature soil-grown plants in which the same Trichoderma strain promotes growth.