Hantavirus in rodents of Buenos Aires Province: are seroprevalence and abundance related?

Oligoryzomys flavescens and Akodon azarae are two rodent species living in agroecosystems of the Pampean region. O. flavescens is a reservoir of the Lechiguanas genotype, associated with Hantavirus Pulmonary Syndrome, whereas Akodon azarae is a reservoir of the Pergamino genotype, which has not been associated with human cases. Our objective was to evaluate whether there is a relationship between abundance and seroprevalence in both rodent species, as this may help to identify situations of high risk of exposure to hantavirus for humans. Eleven longitudinal rodent capture-mark-recapture surveys were conducted in three railway embankments in agricultural landscapes (Exaltación de la Cruz Departament, Buenos Aires province, Argentina), from 2014 through 2016. The trapping effort was 1800 trap-nights per survey. During these surveys, demographic data and blood samples were collected. Blood samples were analyzed by means of ELISAs to determine the presence of hantavirus-specific antibodies. For each rodent species, the relationship between seroprevalence and its abundance was assessed through logit-linked binomial generalized linear models using the number of infected individuals by sampling session as the response variable (i.e., successees, with the corresponding number of tested blood samples per group as trials). Models containing the species’ MNA as a predictor and the null models were evaluated. Using a multi-model approach, averaged parameters and their relative importance were calculated using Akaike weights (AIC). The main finding in this work was that both A. azarae and O. flavescens exhibit a negative relationship between prevalence and abundance. A possible explanation for this result is that populations reach their smaller numbers when these consist mainly of overwintering adults, which had longer exposures with higher chances of becoming infected, whereas larger populations are observed soon after the reproductive season, when new recruits are unlikely to be infected yet. Thus, the effect of prevalence and abundance on the risk of human exposure could be compensatory. This suggests that there would be no particular season of increased risk; prevention and surveillance should be permanent.Para acceder a la videoconferencia completa, hacer clic en "Enlace externo".Sociedad Latinoamericana de Ecología de Vectore

Unconventional pro-inflammatory CD4+ T cell response in B cell-deficient mice infected with Trypanosoma cruzi

Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America but has become a global public health concern by migration of infected people. It has been reported that parasite persistence as well as the intensity of the inflammatory immune response are determinants of the clinical manifestations of the disease. Even though inflammation is indispensable for host defense, when deregulated, it can contribute to tissue injury and organ dysfunction. Here, we report the importance of B cells in conditioning T cell response in T. cruzi infection. Mice deficient in mature B cells (muMT mice) infected with T. cruzi exhibited an increase in plasma TNF concentration, TNF-producing CD4+ T cells, and mortality. The increase in TNF-producing CD4+ T cells was accompanied by a reduction in IFNγ+CD4+ T cells and a decrease of the frequency of regulatory Foxp3+, IL-10+, and IL17+CD4+ T cells populations. The CD4+ T cell population activated by T. cruzi infection, in absence of mature B cells, had a high frequency of Ly6C+ cells and showed a lower expression of inhibitory molecules such as CTLA-4, PD-1, and LAG3. CD4+ T cells from infected muMT mice presented a high frequency of CD62LhiCD44− cells, which is commonly associated with a naïve phenotype. Through transfer experiments we demonstrated that CD4+ T cells from infected muMT mice were able to condition the CD4+ T cells response from infected wild-type mice. Interestingly, using Blimp-flox/flox-CD23icre mice we observed that in absence of plasmablast/plasma cell T. cruzi-infected mice exhibited a higher number of TNF-producing CD4+ T cells. Our results showed that the absence of B cells during T. cruzi infection affected the T cell response at different levels and generated a favorable scenario for unconventional activation of CD4+ T cell leading to an uncontrolled effector response and inflammation. The product of B cell differentiation, the plasmablast/plasma cells, could be able to regulate TNF-producing CD4+ T cells since their absence favor the increase of the number of TNF+ CD4+ in T. cruzi-infected miceResearch reported in this publication was supported by the Agencia Nacional de Promoción Científica y Técnica (Foncyt, PICT 2011-2647 and PICT 2015-0645), Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET, (PIP 112- 20110100378), the Secretaría de Ciencia y Técnica-Universidad Nacional de Córdoba, and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R01AI116432-01

IL-17RA-Signaling Modulates CD8+ T Cell Survival and Exhaustion During Trypanosoma cruzi Infection

The IL-17 family contributes to host defense against many intracellular pathogens by mechanisms that are not fully understood. CD8+ T lymphocytes are key elements against intracellular microbes, and their survival and ability to mount cytotoxic responses are orchestrated by several cytokines. Here, we demonstrated that IL-17RA-signaling cytokines sustain pathogen-specific CD8+ T cell immunity. The absence of IL-17RA and IL-17A/F during Trypanosoma cruzi infection resulted in increased tissue parasitism and reduced frequency of parasite-specific CD8+ T cells. Impaired IL-17RA-signaling in vivo increased apoptosis of parasite-specific CD8+ T cells, while in vitro recombinant IL-17 down-regulated the pro-apoptotic protein BAD and promoted the survival of activated CD8+ T cells. Phenotypic, functional, and transcriptomic profiling showed that T. cruzi-specific CD8+ T cells derived from IL-17RA-deficient mice presented features of cell dysfunction. PD-L1 blockade partially restored the magnitude of CD8+ T cell responses and parasite control in these mice. Adoptive transfer experiments established that IL-17RA-signaling is intrinsically required for the proper maintenance of functional effector CD8+ T cells. Altogether, our results identify IL-17RA and IL-17A as critical factors for sustaining CD8+ T cell immunity to T. cruzi

Estrogen Receptor β-Selective Agonists Stimulate Calcium Oscillations in Human and Mouse Embryonic Stem Cell-Derived Neurons

Estrogens are used extensively to treat hot flashes in menopausal women. Some of the beneficial effects of estrogens in hormone therapy on the brain might be due to nongenomic effects in neurons such as the rapid stimulation of calcium oscillations. Most studies have examined the nongenomic effects of estrogen receptors (ER) in primary neurons or brain slices from the rodent brain. However, these cells can not be maintained continuously in culture because neurons are post-mitotic. Neurons derived from embryonic stem cells could be a potential continuous, cell-based model to study nongenomic actions of estrogens in neurons if they are responsive to estrogens after differentiation. In this study ER-subtype specific estrogens were used to examine the role of ERα and ERβ on calcium oscillations in neurons derived from human (hES) and mouse embryonic stem cells. Unlike the undifferentiated hES cells the differentiated cells expressed neuronal markers, ERβ, but not ERα. The non-selective ER agonist 17β-estradiol (E2) rapidly increased [Ca2+]i oscillations and synchronizations within a few minutes. No change in calcium oscillations was observed with the selective ERα agonist 4,4′,4″-(4-Propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT). In contrast, the selective ERβ agonists, 2,3-bis(4-Hydroxyphenyl)-propionitrile (DPN), MF101, and 2-(3-fluoro-4-hydroxyphenyl)-7-vinyl-1,3 benzoxazol-5-ol (ERB-041; WAY-202041) stimulated calcium oscillations similar to E2. The ERβ agonists also increased calcium oscillations and phosphorylated PKC, AKT and ERK1/2 in neurons derived from mouse ES cells, which was inhibited by nifedipine demonstrating that ERβ activates L-type voltage gated calcium channels to regulate neuronal activity. Our results demonstrate that ERβ signaling regulates nongenomic pathways in neurons derived from ES cells, and suggest that these cells might be useful to study the nongenomic mechanisms of estrogenic compounds

Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

<p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

Morphological changes in Camponotus punctulatus (Mayr) anthills of different ages

In north-eastern Argentina, Camponotus punctulatus builds large numbers of big and coherent anthills after abandonment of rice cultivation. These anthills easily reach 1 m in height and 2 m in diameter, and a density of 1800 nests ha(-1). We studied the internal morphology of C punctulatus aged anthills of 4, 6 and 15 years, respectively, by describing and quantifying, meso- and macroporosity of undisturbed soil samples using image analysis. Four different parts were distinguished on these cone-shaped anthills: the loose granular cortex, the summit, the core of the anthill and the base of the anthill at ground level. The percentage of macroporosity in anthills significantly differed between the parts of the anthill, but changed little with age except for the 15 year old anthill that had increased percentages of mesopores and macropores with rounded and irregular shapes. Walls of the chambers and galleries were highly compacted, highlighting intense ant activity in the anthills, although it was localised mainly in the upper central part. After 6 years the anthills became surrounded by a discontinuous peripheral depression, which likely affects water drainage and infiltration. In 15 year old anthills the lateral depressions became a continuous ditch where water accumulates giving place to a constant wetted zone inside the anthill. Our results support the previous consideration of C punctulatus as an ecosystem engineer, although in this case related to the changes produced on the soil surrounding the anthills which may affect the survival and distribution of other soil organisms. (c) 2005 Elsevier B.V. All rights reserved

CD8+ T Cell Immunity Is Compromised by Anti-CD20 Treatment and Rescued by Interleukin-17A

Monoclonal antibody targeting the CD20 antigen on B cells is used to treat the majority of non-Hodgkin lymphoma patients and some autoimmune disorders. This therapy generates adverse effects, notably opportunistic infections and activation of viruses from latency. Here, using the infection murine model with the intracellular parasite Trypanosoma cruzi, we report that anti-CD20 treatment affects not only B cell responses but also CD8+ T cell responses, representing the most important immune effectors involved in control of intracellular pathogens. Anti-CD20 treatment, directly or indirectly, affects cytotoxic T cell number and function, and this deficient response was rescued by the cytokine IL-17A. The identification of IL-17A as the cytokine capable of reversing the poor response of CD8+ T cells provides information about a potential therapeutic treatment aimed at enhancing defective immunity induced by B cell depletion.Treatment with anti-CD20, used in many diseases in which B cells play a pathogenic role, has been associated with susceptibility to intracellular infections. Here, we studied the effect of anti-CD20 injection on CD8+ T cell immunity using an experimental model of Trypanosoma cruzi infection, in which CD8+ T cells play a pivotal role. C57BL/6 mice were treated with anti-CD20 for B cell depletion prior to T. cruzi infection. Infected anti-CD20-treated mice exhibited a CD8+ T cell response with a conserved expansion phase followed by an early contraction, resulting in a strong reduction in total and parasite-specific CD8+ T cell numbers at 20 days postinfection. Anti-CD20 injection increased the frequency of apoptotic CD8+ T cells, decreased the number of effector and memory CD8+ T cells, and reduced the frequency of proliferating and cytokine-producing CD8+ T cells. Accordingly, infected anti-CD20-treated mice presented lower cytotoxicity of T. cruzi peptide-pulsed target cells in vivo. All of these alterations in CD8+ T cell immunity were associated with increased tissue parasitism. Anti-CD20 injection also dampened the CD8+ T cell response, when this had already been generated, indicating that B cells were involved in the maintenance rather than the induction of CD8+ T cell immunity. Anti-CD20 injection also resulted in a marked reduction in the frequency of interleukin-6 (IL-6)- and IL-17A-producing cells, and recombinant IL-17A (rIL-17A) injection partially restored the CD8+ T cell response in infected anti-CD20-treated mice. Thus, anti-CD20 reduced CD8+ T cell immunity, and IL-17A is a candidate for rescuing deficient responses either directly or indirectly

Pathways as "signatures in landscape": towards an ethnography of mobility among the Mbya-Guaraní (Northeastern Argentina)

RefereedProcesses of spatial mobility among the Mbya are of interest in anthropological and ethnobiological studies, as these processes are related to transformations in the landscape and the environment. Despite this, ethnographic literature usually focuses itself on the mobility of Guaraní communities from the perspective of population dynamics on a regional scale. Our research among two Mbya-Guaraní communities in the Argentinean province of Misiones has enabled us to recognize patterns of mobility on a micro-scale. Certainly, the mobility of adult members of these communities as they perform hunting and gathering activities delimit spaces of individual use. We consider the different pathways as "signatures in landscape", resulting from processes of spatial mobility inherent to those activities Taking into account the gathering and circulation of medicinal plants for treatment of gastrointestinal illnesses, we have been able to identify different pathways inherent in their search, towards the monte or other spaces away from de settlement. The design and construction of the pathways is determined by the specific personal knowledge of individuals who search for these valuable resources. Using both strategies of direct observation – as members of the community manipulate different resources during these search and gathering trips – and interviews, we have been able to gather and interpret significant information on the strategies used by the Mbya to domesticate the monte areas. As a consequence of our approach we suggest that the landscape design resulting from these trips should not be considered a consensual or collective strategy of the whole community; it is rather the result of the daily strategies of individuals, which involves the selection of resources mainly based on each individual's knowledge and interests.Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Universidad Nacional de La Plat