Impact of the mites Dermanyssus gallinae and Tyrophagus putrescentiae on production and health of laying hens.

Mites are considered a threat to the commercial poultry industry due to their direct and indirect pathogenic effects. Dermanyssus gallinae is among the mite species that endanger production, as it is hematophagous and poses a serious sanitary risk. Recently, Tyrophagus putrescentiae has also drawn attention as a potential pest in the poultry industry, and its attacks have been related to clinical symptoms such as cutaneous eruptions and bird restlessness. Considering the potential economic, sanitary, and productive losses both species represent to the laying-hen industry, the aim of the present study was to evaluate the influence of D. gallinae and T. putrescentiae on the health and productivity of commercial laying hens by carrying out infestation experiments and by monitoring laying hens for a period of 60 days. Tyrophagus putrescentiae and D. gallinae affected egg quality and zootechnical parameters in laying hens. Hens infested by T. putrescentiae had behavioral changes, weight loss, stress symptoms, and decreased egg laying and quality, as well as diarrhea, gradual feather loss, and itching. Hens infested by D. gallinae also had weight loss, behavioral changes, and stress symptoms, leading to decreased laying and egg quality. The present study proposes an experimental model to understand the impacts caused by T. putrescentiae and D. gallinae on commercial laying production and egg quality parameters.

Highly Efficient CRISPR/Cas9 Mediated Gene Editing in Ocimum basilicum 'FT Italiko' to Induce Resistance to Peronospora belbahrii.

Ocimum basilicum (sweet basil) is an economically important aromatic herb; in Italy, approximately 1000 ha of "Genovese-type" basil are grown annually in greenhouses and open fields and are subjected to Downy Mildew (DM) disease, caused by Peronospora belbahrii, leading to huge crop losses. Mutation of the Susceptibility (S) gene DMR6 (Downy Mildew Resistant 6) has been proven to confer a broad-spectrum resistance to DM. In this work, an effective Genome Editing (GE) approach mediated by CRISPR/Cas9 in O. basilicum 'Italiko', the élite cultivar used to produce "Pesto Genovese D.O.P", was developed. A highly efficient genetic transformation method mediated by A. tumefaciens has been optimized from cotyledonary nodes, obtaining 82.2% of regenerated shoots, 84.6% of which resulted in Cas9+ plants. Eleven T0 lines presented different type of mutations in ObDMR6; 60% were indel frameshift mutations with knock-out of ObDMR6 of 'FT Italiko'. Analysis of six T1 transgene-free seedlings revealed that the mutations of T0 plants were inherited and segregated. Based on infection trials conducted on T0 plants, clone 22B showed a very low percentage of disease incidence after 14 days post infection. The aromatic profile of all in vitro edited plants was also reported; all of them showed oxygenated monoterpenes as the major fraction.

Effects of in-house and commercial extracts of the allergenic mite Tyrophagus putrescentiae on murine and human cell responses.

Mites are among the major sources of domestic and occupational allergens worldwide, and continuous exposure to these allergens leads to chronic airway inflammation. One of the most allergenic species is the storage mite Tyrophagus putrescentiae (Schrank). Protein extracts are produced from this mite for tests that help the clinical diagnosis (via prick test), treatment, and monitoring of disease progression in patients who had positive results for allergic reactions. Therefore, the aim of the present study was to evaluate the cell viability of RAW 264.7 and L929 cells when exposed to in-house raw protein extracts of T. putrescentiae compared to a commercial product, as well as quantify TNF-α secretion by RAW 264.7. Additionally, this study quantified the effect of these extracts in IgE secretion in total blood of people affected by this mite. The study found similarity between the in-house extract and the commercial extract as they had equivalent TNF-α secretion. Additionally, viabilities of RAW 264.7 and L929 exposed to the in-house extract were compatible with viabilities of cells exposed to the commercial extract, with no cytotoxicity at the concentrations tested. Results corroborated the hypothesis that the extract produced in-house would be equivalent to the commercial extract in allergic patients when the IgE was quantified. This study is the first to show the cytotoxicity of T. putrescentiae extracts, and to provide a quantitative analysis of TNF-α and IgE.

Grief, mourning, and the body: Ritual attention to the death of victims of the dictatorship in Chile.

This study considers the way in which the recovery of the bodies of those who were detained and disappeared under the Pinochet dictatorship not only enables the social recognition of their deaths and the performance of death rituals hitherto obstructed, but also makes it possible to "attend to" their deaths in multiple dimensions. The research draws upon testimonies and records collected during fieldwork for an ongoing anthropological investigation. We observe the different practices that can be associated with the process of "dignification," including the physical demonstrations of affection made possible by the recovery of the bodies. We also illustrate how, for family members, the practices involved in "caring for" and "attending to" death may defy or test the limits of standardized processes imposed by professionals and preconceived ideas or practices relating to death.

Retrospective molecular investigation of Mayaro and Oropouche viruses at the human-animal interface in West-central Brazil, 2016-2018.

Mayaro virus (MAYV, Togaviridae) and Oropouche orthobunyavirus (OROV, Peribunyaviridae) are emerging enzootic arboviruses in Latin America. Outbreaks of febrile illness associated with MAYV and OROV have been reported among humans mainly in the northern region of Brazil since the 1980s, and recent data suggest these viruses have circulated also in more populated areas of western Brazil. MAYV shares mosquito vectors with yellow fever virus and it has been historically detected during yellow fever epidemics. Aiming to investigate the transmission of OROV and MAYV at the human-animal interface during a yellow fever, chikungunya and Zika outbreaks in Brazil, we conducted a retrospective molecular investigation in 810 wild and domestic animals, 106 febrile patients, and 22.931 vectors collected from 2016 to 2018 in Cuiaba and Campo Grande metropolitan regions, western Brazil. All samples tested negative for OROV and MAYV RNA by RT-qPCR. Findings presented here suggest no active circulation of MAYV and OROV in the sampled hosts. Active surveillance and retrospective investigations are instrumental approaches for the detection of cryptic and subclinical activity of enzootic arboviruses and together serve as a warning system to implement appropriate actions to prevent outbreaks.

Linum lewisii Adventitious and Hairy-Roots Cultures as Lignan Plant Factories.

Plants synthesize specific secondary metabolites for survival, reproduction, environmental resilience, and defense. Among them, lignans are a class of polyphenols with several bioactive properties: chemopreventive, anti-inflammatory, antiviral, and antioxidant. These compounds are often extracted from field-grown plants with very low yields. To overcome these constraints, in vitro tissue cultures provide a tool to optimize large-scale production. Moreover, the use of elicitation to increase secondary metabolite production is gaining importance. The aim of this work was to develop adventitious (ARL) and hairy roots (HRL) from Linum lewisi, a species able to synthesize arylnaphthalene lignans such as justicidin B. The ARL and HRL were obtained for the first time and characterized for their phenol content, antioxidant activity, and the production of justicidin B after treatments with several elicitors and precursor feeding. Through NMR spectroscopy, other four lignans were highlighted and identified in the roots extracts. A pilot-scale bioreactor was adopted to assess the suitability of the developed root cultures for future large-scale production. The ARL and HRL cultures showed a justicidin B production higher than other Linum species cultures described up to now (75.8 mg/L and 82.2 g/L), and the production more than doubled after elicitation with MeJA.

Optimized Ultrasound-Assisted Extraction of Lignans from Linum Species with Green Solvents.

Lignans are plant phenols derived from phenylpropanoids. They play a significant role in plant defense and have features that make them appealing for pharmaceutical applications. Lignans can be obtained by plant in vitro cultures; their production by adventitious and hairy roots of Linum species seems to be a promising alternative to chemical synthesis. In the context of large-scale production, it is necessary to optimize their extraction from plants tissue by choosing the more suitable solvent and extraction procedure, paying attention to the use of green media and methods. With the aim to select the best conditions for the extraction of two interesting lignans (justicidin B and 6-methoxypodophyllotoxin) from Linum tissues, different green solvents and the method of ultrasound-assisted extraction were tested. The results showed that ethyl methyl ketone and dimethyl carbonate were the best media to extract justicidin B and 6-methoxypodophyllotoxin, respectively, in terms of purity and recovery. Moreover, we showed that ultrasound-assisted extraction presents different advantages compared to conventional methods. Finally, the optimal experimental conditions to extract justicidin B from L. austriacum hairy roots using methyl ethyl ketone were also determined by the response surface method. The models obtained are reliable and accurate to estimate the purity and recovery of justicidin B.

Behavioural factors underlying innovative problem-solving differences in an avian predator from two contrasting habitats.

Innovative behavior is considered one of the main factors facilitating the adaptation of animals to urban life. However, the relationship between urbanization and innovativeness is equivocal, perhaps reflecting aspects of urban environments that influence differently the behavioural traits underlying the occurrence of an innovation. In this work, we analysed the variation in innovative problem-solving performance between urban and rural individuals of the Caracara Chimango (Milvago chimango), with the goal of determining which behavioural trait (or combination) most explained such variation. We found that urban raptors outperformed rural ones in their solving speed and solving level (number of solutions) with a multiaccess box. They also showed more persistence, motor flexibility and diversity, as well as higher effectiveness in their solving attempts than rural chimangos. Sex was not an important factor. Urban chimangos showed less neophobia and spent more time exploring the box than rural birds during the initial habituation period, which probably determined the amount of information about the system that each individual had at the beginning of first problem solving trial. This difference in novelty response both directly and indirectly, through its relationship with persistence, motor flexibility and proportion of effective attempts, explained variability in solving performance. All individuals showed a decrease in solving latency, and an increase in solving level with experience, indicating that learning occurred in both raptor groups. This improvement occurred in parallel with changes in the afore-mentioned traits, though the pattern of improvement differed between urban and rural chimangos. We suggest that the characteristics of urban areas modulate the novelty response of chimangos, along with other correlated non-cognitive behavioural traits, which act in combination to increase the chances that novel problems could be quickly solved, and the resulting new behaviours established in city populations of this species.

Innovative problem-solving in a threatened gull species, the Olrog's Gull (Larus atlanticus).

Innovation, a process that plays an important role in the ecology and evolution of species, is considered an expression of behavioral flexibility in animals. Here we analyzed innovative problem-solving ability and performance enhancement through learning in the Olrog's Gull (Larus atlanticus), under controlled processes and experimental conditions. Trials were undertaken with nine adult individuals captured at a highly urbanized coastal area of Argentina. Each individual was presented with a Plexiglas box that could be opened by pushing or pulling two lids, each lid leading to a separated food reward. We measured problem-solving ability through consumption latency and the number of solved lids. As explanatory variables, we measured contact rate, as a measure of persistence, and the number of effective contacts. The results showed that the contact rate and effective contacts did not affect variables related to problem-solving ability during the first confrontation of the individuals with the closed box. Consumption latency decreased significantly throughout the trials, and with increasing contact rate and effective contacts. The number of solved lids increased through the trials independently of the contact rate and the total effective contacts with the box. Although persistence did not influence individuals' performance during the problem-solving test; this variable affected individuals' ability to solve the task throughout trials. Learning was evidenced by the decrease in the resolution time across experiments, suggesting that successful individuals improved their performance probably through a trial-and-error process. Evaluation of behavioral responses of a threatened seabird to a novel problem-solving task adds knowledge to previous field studies and provides a better understanding of the ability of individuals to adjust their foraging behavior in highly urbanized areas used during the non-breeding season.

Sialovirome of Brazilian tropical anophelines.

Anophelinae is a widely dispersed Culicidae subfamily that may carry a unique virome. Here we herein report the set of viruses found in 323 salivary glands of 16 anopheline species sampled at Upper Pantanal, Chapada dos Guimarães National Park and Coxipó river basin, South Central Mato Grosso, Brazil, pooled (n = 11) and subjected to high throughput sequencing. Metagenomics revealed the presence of nine viral sequences belonging to novel viruses from seven viral families: Purunga is a putative novel orbivirus sharing 74% and 65% aa identity, respectively, with the VP1 and VP3 segments of Changuinola serogroup, Jaracatiá flavivirus shares 60% amino-acid (aa) identity with Aedes flavivirus. Coxipó dielmovirus and Chapada dielmovirus shared 51% and 39% aa identity with Merida virus. Coloiado-orthomyxo like virus is 57.1-64.8% identical at aa level to Aedes albonnulatus orthomyxo-like virus. Mujica picorna-like virus shares 49% aa identity with Flen picorna-like virus and Chiquitos virus is 50% similar to Ista virus, both from Picornavirales order. Cerrado partiti-like-virus shares 75-86% aa identity with Atrato partiti-like virus 2. We also found the S and L segments of Anopheles triannulatus orthophasmavirus (92% identity) in Anopheles lutzi from Chapada dos Guimarães. The identification of these putative novel viruses underscore the wide dispersion of viruses in culicid hosts contributing to extensions on mosquito virome descriptions.

New Insight into Justicidin B Pathway and Production in Linum austriacum.

Lignans are the main secondary metabolites synthetized by Linum species as plant defense compounds but they are also valuable for human health, in particular, for novel therapeutics. In this work, Linum austriacum in vitro cultures, cells (Cc), adventitious roots (ARc) and hairy roots (HRc) were developed for the production of justicidin B through elicitation with methyl jasmonate (MeJA) and coronatine (COR). The performances of the cultures were evaluated for their stability, total phenols content and antioxidant ability. NMR was used to identify justicidin B and isojusticidin B and HPLC to quantify the production, highlighting ARc and HRc as the highest productive tissues. MeJA and COR treatments induced the synthesis of justicidin B more than three times and the synthesis of other compounds. RNA-sequencing and a de novo assembly of L. austriacum ARc transcriptome was generated to identify the genes activated by MeJA. Furthermore, for the first time, the intracellular localization of justicidin B in ARc was investigated through microscopic analysis. Then, HRc was chosen for small-scale production in a bioreactor. Altogether, our results improve knowledge on justicidin B pathway and cellular localization in L. austriacum for future scale-up processes.

Case report: Tyrophagus putrescentiae (Acari) attacking laying birds in conventional poultry houses.

Tyrophagus putrescentiae (Schrank) (Acaridae) is one of the most allergenic mite species worldwide, and it particularly infests household environments, animal feed factories, and food factories. It has been the aim of several studies recently in the healthcare area due to its allergenic potential. However, there had been no records of this species attacking laying birds until this report. This is the first record of adverse reactions in animals triggered by infestations of this species. Therefore, the present study aims at describing the damages and symptomatology of T. putrescentiae infestations on commercial laying hens. Alopecia and dermatitis were symptoms exacerbated by T. putrescentiae infestation starting at 40 weeks old. The presence of this species on hens, as observed in the present study, might be directly related to the accumulation of food and poultry litter on these birds, in their cages, or in the vicinities. Hence, the results might be related to their feeding behavior, which consists of continuous supply of animal feed in these management systems. The present study provides an unprecedented record that reveals the importance and potential for emergency pest status of T. putrescentiae in the poultry industry. Its infestations in poultry houses probably required constant sanitary care and monitoring are required in order to prevent outbreaks of this mite.

The Double-Layer Method to the Genesis of Androgenic Plants in Anemone coronaria.

Homozygous lines occur for plant breeding programs and for studies about gene expression and genetic mapping and they can be derived from anther culture. In this chapter, the method to obtain androgenic plants from an ornamental cut flower, Anemone coronaria belonging to the Ranunculaceae family, is described. In this species, androgenic plants were obtained culturing anthers with responsive microspores in Petri dishes containing a double layer of substrate with specific composition. Moreover, thermic treatment has been applied to induce the switch from pollen development program to embryo development program. The method allows to produce both double-haploid plants from diploid mothers (2n) and di-haploid plants from tetraploid mothers (4n).

Genetic Improvement of Arundo donax L.: Opportunities and Challenges.

Arundo donax L., the giant reed-being a long-duration, low-cost, non-food energy crop able to grow in marginal lands-has emerged as a potential alternative to produce biomass for both energy production, with low carbon emissions, and industrial bioproducts. In recent years, pioneering efforts have been made to genetically improve this very promising energy crop. This review analyses the recent advances and challenges encountered in using clonal selection, mutagenesis/somaclonal variation and transgenesis/genome editing. Attempts to improve crop yield, in vitro propagation efficiency, salt and heavy metal tolerance by clonal selection were carried out, although limited by the species' low genetic diversity and availability of mutants. Mutagenesis and somaclonal variation have also been attempted on this species; however, since Arundo donax is polyploid, it is very difficult to induce and select promising mutations. In more recent years, genomics and transcriptomics data are becoming available in Arundo, closing the gap to make possible the genetic manipulation of this energy crop in the near future. The challenge will regard the functional characterization of the genes/sequences generated by genomic sequencing and transcriptomic analysis in a complex polyploid genome.

Stabilization of Glycosylated ß-Glucosidase by Intramolecular Crosslinking Between Oxidized Glycosidic Chains and Lysine Residues.

Many industrial enzymes can be highly glycosylated, including the ß-glucosidase enzymes. Although glycosylation plays an important role in many biological processes, such chains can cause problems in the multipoint immobilization techniques of the enzymes, since the glycosylated chains can cover the reactive groups of the protein (e.g., Lys) and do not allow those groups to react with reactive groups of the support (e.g., aldehyde and epoxy groups). Nevertheless, the activated glycosylated chains can be used as excellent crosslinking agents. The glycosylated chains when oxidized with periodate can generate aldehyde groups capable of reacting with the amino groups of the protein itself. Such intramolecular crosslinks may have significant stabilizing effects. In this study, we investigated if the intramolecular crosslinking occurs in the oxidized ß-glucosidase and its effect on the stability of the enzyme. For this, the oxidation of glycosidic chains of ß-glucosidase was carried out, allowing to demonstrate the formation of aldehyde groups and subsequent interaction with the amine groups and to verify the stability of the different forms of free enzyme (glycosylated and oxidized). Furthermore, we verified the influence of the glycosidic chains on the immobilization of ß-glucosidase from Aspergillus niger and on the consequent stabilization. The results suggest that intramolecular crosslinking occurred and consequently the oxidized enzyme showed a much greater stabilization than the native enzyme (glycosylated). When the multipoint immobilization was performed in amino-epoxy-agarose supports, the stabilization of the oxidized enzyme increases by a 6-fold factor. The overall stabilization strategy was capable to promote an enzyme stabilization of 120-fold regarding to the soluble unmodified enzyme.

Novel Viruses in Mosquitoes from Brazilian Pantanal.

Viruses are ubiquitous and diverse microorganisms arising as a result of interactions within their vertebrate and invertebrate hosts. Here we report the presence of different viruses in the salivary glands of 1657 mosquitoes classified over 28 culicinae species from the North region of the Brazilian Pantanal wetland through metagenomics, viral isolation, and RT-PCR. In total, 12 viruses were found, eight putative novel viruses with relatively low similarity with pre-existing species of viruses within their families, named Pirizal iflavirus, Furrundu phlebovirus, Pixé phlebovirus, Guampa vesiculovirus, Chacororé flavivirus, Rasqueado orbivirus, Uru chuvirus, and Bororo circovirus. We also found the already described Lobeira dielmorhabdovirus, Sabethes flavivirus, Araticum partitivirus, and Murici totivirus. Therefore, these findings underscore the vast diversity of culicinae and novel viruses yet to be explored in Pantanal, the largest wetland on the planet.

Monocyte glycolysis determines CD8+ T cell functionality in human Chagas disease.

Chagas disease is a lifelong pathology resulting from Trypanosoma cruzi infection. It represents one of the most frequent causes of heart failure and sudden death in Latin America. Herein, we provide evidence that aerobic glycolytic pathway activation in monocytes drives nitric oxide (NO) production, triggering tyrosine nitration (TN) on CD8+ T cells and dysfunction in patients with chronic Chagas disease. Monocytes from patients exhibited a higher frequency of hypoxia-inducible factor 1α and increased expression of its target genes/proteins. Nonclassical monocytes are expanded in patients' peripheral blood and represent an important source of NO. Monocytes entail CD8+ T cell surface nitration because both the frequency of nonclassical monocytes and that of NO-producing monocytes positively correlated with the percentage of TN+ lymphocytes. Inhibition of glycolysis in in vitro-infected peripheral blood mononuclear cells decreased the inflammatory properties of monocytes/macrophages, diminishing the frequency of IL-1ß- and NO-producing cells. In agreement, glycolysis inhibition reduced the percentage of TN+CD8+ T cells, improving their functionality. Altogether, these results clearly show that glycolysis governs oxidative stress on monocytes and modulates monocyte-T cell interplay in human chronic Chagas disease. Understanding the pathological immune mechanisms that sustain an inflammatory environment in human pathology is key to designing improved therapies.

Optimization and validation of simultaneous analyses of ecgonine, cocaine, and seven metabolites in human urine by gas chromatography-mass spectrometry using a one-step solid-phase extraction.

The presence of ecgonine in urine has been proposed as an appropriate marker of cocaine use. Only a few methods have been published for their determination along with cocaine and the rest of its metabolites. Due to their high polarity and consequent solubility in water, these have low recoveries, which is why it is necessary to increase the sensitivity, by the formation of hydrochloric salts or multiderivatization of the analytes or by performing two solid-phase extractions (SPEs), considerably increasing the time and cost of the analysis. This work describes a fast and fully validated procedure for the simultaneous detection and quantification of ecgonine, ecgonine-methyl-ester, benzoylecgonine, nor-benzoylecgonine, m-hydroxybenzoylecgonine, cocaethylene, cocaine, norcocaine, and norcocaethylene in human urine (500 µL) using one SPE and simple derivatization. Separation and quantification were achieved by gas chromatography-electron ionization-mass spectrometry (GC-EI-MS) in selected-ion monitoring mode. Quantification was performed by the addition of deuterated analogs as internal standards. Calibration curves were linear in the adopted ranges, with determination coefficients higher than 0.99. The lower limits of quantification ranged from 2.5 to 10 ng/mL. The intra- and inter-day precision, calculated in terms of relative standard deviation, were 1.2%-14.9% and 1.8%-17.9%, respectively. The accuracy, in terms of relative error, was within a ± 16.4% interval. Extraction efficiency ranged from 84% to 103%. Compared with existing methods, the procedure described herein is fast, since only one SPE is required, and cost-effective. In addition, this method provides a high recovery for ecgonine, resulting in a better alternative to the previously published methods.

Neophobia is negatively related to reversal learning ability in females of a generalist bird of prey, the Chimango Caracara, Milvago chimango.

In an ever-changing environment, the ability to adapt choices to new conditions is essential for daily living and ultimately, for survival. Behavioural flexibility allows animals to maximise survival and reproduction in novel settings by adjusting their behaviour based on specific information and feedback acquired in their current environments. However, a growing body of evidence indicates that an individual's personality type can limit the extent to which the individual might behave flexibly, by influencing the way an individual pays attention to novelty and how much information it collects and stores, which in turn affects the individual's decision-making and learning process. In this study, the behavioural flexibility of a generalist predator, the Chimango Caracara, Milvago chimango, was analysed using the reversal learning paradigm, focusing on the comparison between age classes, and the relation of learning flexibility with a personality trait, the level of neophobia. Due to the low number of male individuals captured, this study was carried out only with female birds. The results showed that age had no significant effect either on the acquisition of a stimulus-reward association, or on the capacity of reversing this previously learned association. Reversal of the response was a harder task for these birds in comparison with the initial acquisition process. The individual's performances in the learning tasks seemed to be uncorrelated with each other, suggesting that they involve different neural mechanisms. Contrary to the general pattern observed in the majority of previous work on personality and cognition in non-human animals, the level of neophobia did not correlate with the initial associative learning performance in both adults and juveniles, yet it showed a significant negative relationship with reversal learning ability, mainly in the regressive phase of this task, for the two age classes. Our results suggest that the predatory and generalist lifestyle of female individuals of M. chimango along with the selective pressures of the environment of the individuals studied might play a critical role in the degree and direction of the linkage between novelty response and learning flexibility observed in this study.

IL-6 Improves the Nitric Oxide-Induced Cytotoxic CD8+ T Cell Dysfunction in Human Chagas Disease.

Reactive oxygen and nitrogen species are important microbicidal agents and are also involved in lymphocyte unresponsiveness during experimental infections. Many of the biological effects attributed to nitric oxide are mediated by peroxynitrites, which induce the nitration of immune cells, among others. Our group has demonstrated that nitric oxide is involved in the suppressive activity of myeloid-derived suppressor cells in Trypanosoma cruzi-infected mice, with a higher number of CD8+ T cells suffering surface-nitration compared to uninfected controls. Studying the functional and phenotypic features of peripheral CD8+ T cells from chagasic patients and human cells experimentally infected with T. cruzi, we found that different regulatory mechanisms impaired the effector functions of T cytotoxic population from seropositive patients. Peripheral leukocytes from chagasic patients showed increased nitric oxide production concomitant with increased tyrosine nitration of CD8+ T cells. Additionally, this cytotoxic population exhibited increased apoptotic rate, loss of the TCRζ-chain, and lower levels of CD107a, a marker of degranulation. Strikingly, IL-6 stimulation of in vitro-infected peripheral blood mononuclear cells obtained from healthy donors, blunted T. cruzi-induced nitration of CD3+CD8+ cells, and increased their survival. Furthermore, the treatment of these cultures with an IL-6 neutralizing antibody increased the percentage of T. cruzi-induced CD8+ T cell nitration and raised the release of nitric oxide. The results suggest that the under-responsiveness of cytotoxic T cell population observed in the setting of long-term constant activation of the immune system could be reverted by the pleiotropic actions of IL-6, since this cytokine improves its survival and effector functions.