Deterioration of Organ Function As a Hallmark in Sepsis: The Cellular Perspective.

Development of organ dysfunction discriminates sepsis from uncomplicated infection. The paradigm shift implicated by the new sepsis-3 definition holds that initial impairment of any organ can pave the way for multiple organ dysfunction and death. Moreover, the role of the systemic inflammatory response, central element in previous sepsis definitions, has been questioned. Most strikingly, a so far largely underestimated defense mechanism of the host, i.e., "disease tolerance," which aims at maintaining host vitality without reducing pathogen load, has gained increasing attention. Here, we summarize evidence that a dysregulation of critical cellular signaling events, also in non-immune cells, might provide a conceptual framework for sepsis-induced dysfunction of parenchymal organs in the absence of significant cell death. We suggest that key signaling mediators, such as phosphoinositide 3-kinase, mechanistic target of rapamycin, and AMP-activated protein kinase, control the balance of damage and repair processes and thus determine the fate of affected organs and ultimately the host. Therapeutic targeting of these multifunctional signaling mediators requires cell-, tissue-, or organ-specific approaches. These novel strategies might allow stopping the domino-like damage to further organ systems and offer alternatives beyond the currently available strictly supportive therapeutic options.

Robotic mechanical wounding (MecWorm) versus herbivore-induced responses: early signaling and volatile emission in Lima bean (Phaseolus lunatus L.).

Insect herbivory on plants is a complex incident consisting of at least two different aspects, mechanical damage and chemical factors. Only the combination of both is able to induce the respective plant defenses. Thus, diverse plant species emit volatile organic compounds (VOCs) in response to herbivory (HW), whereas mechanical damage inflicted as single wounding event (MD) does not induce increased VOC emissions. In contrast, a robotic worm (MecWorm, MW) allowed demonstrating that continuous mechanical damage is sufficient to induce volatile emission in Lima bean. However, the induced VOC blends remain characteristic for the respective stimulus. In order to identify putative differences in plant signaling leading to defenses, we compared time courses of early signals induced by wounding in Lima bean. Neither MD nor MW alone was able to induce plasma membrane (V (m)) depolarization, as observed after Spodoptera littoralis HW, but V (m) depolarization occurred in both treatments when used in combination with herbivore-derived oral secretions. A significant increase in cytosolic Ca(2+) concentrations was observed only after HW, whereas MD and MW did not affect this second messenger. H(2)O(2) was generated within 2-3 h after leaf damage by HW and MW, whereas MD induced only half of the H(2)O(2) levels compared to the other treatments. Both HW and MW induced a marked accumulation of NO, but with distinct temporal patterns. NO production after MD followed the same trend but reached significantly lower values. The results indicate that chemical signals from the herbivores are responsible for the induction of the earliest signaling events. These changes appear to be characteristic for the reaction to herbivory.

Does mycorrhization influence herbivore-induced volatile emission in Medicago truncatula?

Symbiosis with mycorrhizal fungi substantially impacts secondary metabolism and defensive traits of colonised plants. In the present study, we investigated the influence of mycorrhization (Glomus intraradices) on inducible indirect defences against herbivores using the model legume Medicago truncatula. Volatile emission by mycorrhizal and non-mycorrhizal plants was measured in reaction to damage inflicted by Spodoptera spp. and compared to the basal levels of volatile emission by plants of two different cultivars. Emitted volatiles were recorded using closed-loop stripping and gas chromatography/mass spectrometry. The documented volatile patterns were evaluated using multidimensional scaling to visualise patterns and stepwise linear discriminant analysis to distinguish volatile blends of plants with distinct physiological status and genetic background. Volatile blends emitted by different cultivars of M. truncatula prove to be clearly distinct, whereas mycorrhization only slightly influenced herbivore-induced volatile emissions. Still, the observed differences were sufficient to create classification rules to distinguish mycorrhizal and non-mycorrhizal plants by the volatiles emitted. Moreover, the effect of mycorrhization turned out to be opposed in the two cultivars examined. Root symbionts thus seem to alter indirect inducible defences of M. truncatula against insect herbivores. The impact of this effect strongly depends on the genetic background of the plant and, hence, in part explains the highly contradictory results on tripartite interactions gathered to date.

NO signals in the haze: nitric oxide signalling in plant defence.

Nitric oxide (NO) is gaining increasing attention as a regulator of diverse (patho-)physiological processes in plants. Although this molecule has been described as playing a role in numerous conditions, its production, turnover and mode of action are poorly understood. Recent studies on NO production have tended to highlight the questions that still remain unanswered rather than telling us more about NO metabolism. But regarding NO signalling and functions, new findings have given an impression of the intricacy of NO-related signalling networks. Different targets of protein S-nitrosylation have been characterised and enzymatic routes controlling this posttranslational modification are emerging, along with their physiological implications. Evidence is also accumulating for protein tyrosine nitration and cGMP as important components of NO-related signal transduction.

Microbial oligosaccharides differentially induce volatiles and signalling components in Medicago truncatula.

Plants perceive biotic stimuli by recognising a multitude of different signalling compounds originating from the interacting organisms. Some of these substances represent pathogen-associated molecular patterns, which act as general elicitors of defence reactions. But also beneficial microorganisms like rhizobia take advantage of compounds structurally related to certain elicitors, i.e. Nod-factors, to communicate their presence to the host plant. In a bioassay-based study we aimed to determine to what extent distinct oligosaccharidic signals are able to elicit overlapping responses, including the emission of volatile organic compounds which is mainly considered a typical mode of inducible indirect defence against herbivores. The model legume Medicago truncatula Gaertn. was challenged with pathogen elicitors (beta-(1,3)-beta-(1,6)-glucans and N,N',N'',N'''-tetraacetylchitotetraose) and two Nod-factors, with one of them being able to induce a nodulation response in M. truncatula. Single oligosaccharidic elicitors caused the emission of volatile organic compounds, mainly sesquiterpenoids. The volatile blends detected were quite characteristic for the applied compounds, which could be pinpointed by multivariate statistical methods. As potential mediators of this response, the levels of jasmonic acid and salicylic acid were determined. Strikingly, neither of these phytohormones exhibited changing levels correlating with enhanced volatile emission. All stimuli tested caused an overproduction of reactive oxygen species, whereas nitric oxide accumulation was only effected by elicitors that were equally able to induce volatile emission. Thus, all signalling compounds tested elicited distinct reaction patterns. However, similarities between defence reactions induced by herbivory and pathogen-derived elicitors could be ascertained; but also Nod-factors were able to trigger defence-related reactions.

Herbivore-induced terpenoid emission in Medicago truncatula: concerted action of jasmonate, ethylene and calcium signaling.

Plant volatiles emitted by Medicago truncatula in response to feeding larvae of Spodoptera exigua are composed of a complex blend of terpenoids. The cDNAs of three terpene synthases (TPSs), which contribute to the blend of terpenoids, were cloned from M. truncatula. Their functional characterization proved MtTPS1 to be a beta-caryophyllene synthase and MtTPS5 to be a multi-product sesquiterpene synthase. MtTPS3 encodes a bifunctional enzyme producing (E)-nerolidol and geranyllinalool (precursors of C11 and C16 homoterpenes) from different prenyl diphosphates serving as substrates. The addition of jasmonic acid (JA) induced expression of the TPS genes, but terpenoid emission was higher from plants treated with JA and the ethylene precursor 1-amino-cyclopropyl-1-carboxylic acid. Compared to infested wild-type M. truncatula plants, lower amounts of various sesquiterpenes and a C11-homoterpene were released from an ethylene-insensitive mutant skl. This difference coincided with lower transcript levels of MtTPS5 and of 1-deoxy-D: -xylulose-5-phosphate synthase (MtDXS2) in the damaged skl leaves. Moreover, ethephon, an ethylene-releasing compound, modified the extent and mode of the herbivore-stimulated Ca2+ variations in the cytoplasm that is necessary for both JA and terpene biosynthesis. Thus, ethylene contributes to the herbivory-induced terpenoid biosynthesis at least twice: by modulating both early signaling events such as cytoplasmic Ca2+-influx and the downstream JA-dependent biosynthesis of terpenoids.

Direct and indirect defences induced by piercing-sucking and chewing herbivores in Medicago truncatula.

Direct and indirect defences against feeding induced by chewing (Spodoptera littoralis) and piercing-sucking (Tetranychus urticae) herbivores, as well as components of signal transduction, were investigated in the model legume Medicago truncatula. Emitted volatiles, representing a mechanism of indirect defence, were measured and identified by gas chromatography/mass spectrometry (GC-MS). As elements of direct defence, the accumulation of phenolic compounds and of reactive oxygen species (ROS) was assessed using microscopic techniques. Jasmonic acid (JA) and salicylic acid (SA) concentrations were assessed as putative components of signal transduction. Volatile profiles revealed a sizeable number of different substances emitted, particularly sesquiterpenoids. The qualitative composition clearly differed depending on the type of herbivory. The same held true for JA and SA concentrations. Also, deposition of phenolic compounds and the production of ROS around the wounding sites could be detected. Conspicuous differences were found in indirect defence and signalling for different types of herbivory. In contrast, no divergence in direct defences was observed; furthermore, the traits investigated exhibited striking similarities to reactions known to occur upon pathogen attack.