Alarmin S100A11 initiates a chemokine response to the human pathogen Toxoplasma gondii.

Toxoplasma gondii is a common protozoan parasite that infects up to one third of the world's population. Notably, very little is known about innate immune sensing mechanisms for this obligate intracellular parasite by human cells. Here, by applying an unbiased biochemical screening approach, we show that human monocytes recognized the presence of T. gondii infection by detecting the alarmin S100A11 protein, which is released from parasite-infected cells via caspase-1-dependent mechanisms. S100A11 induced a potent chemokine response to T. gondii by engaging its receptor RAGE, and regulated monocyte recruitment in vivo by inducing expression of the chemokine CCL2. Our experiments reveal a sensing system for T. gondii by human cells that is based on the detection of infection-mediated release of S100A11 and RAGE-dependent induction of CCL2, a crucial chemokine required for host resistance to the parasite.

T-bet-dependent ILC1- and NK cell-derived IFN-γ mediates cDC1-dependent host resistance against Toxoplasma gondii.

Host resistance against intracellular pathogens requires a rapid IFN-γ mediated immune response. We reveal that T-bet-dependent production of IFN-γ is essential for the maintenance of inflammatory DCs at the site of infection with a common protozoan parasite, Toxoplasma gondii. A detailed analysis of the cellular sources for T-bet-dependent IFN-γ identified that ILC1s and to a lesser degree NK, but not TH1 cells, were involved in the regulation of inflammatory DCs via IFN-γ. Mechanistically, we established that T-bet dependent innate IFN-γ is critical for the induction of IRF8, an essential transcription factor for cDC1s. Failure to upregulate IRF8 in DCs resulted in acute susceptibility to T. gondii infection. Our data identifies that T-bet dependent production of IFN-γ by ILC1 and NK cells is indispensable for host resistance against intracellular infection via maintaining IRF8+ inflammatory DCs at the site of infection.

TLR11-independent inflammasome activation is critical for CD4+ T cell-derived IFN-γ production and host resistance to Toxoplasma gondii.

Innate recognition of invading intracellular pathogens is essential for regulating robust and rapid CD4+ T cell effector function, which is critical for host-mediated immunity. The intracellular apicomplexan parasite, Toxoplasma gondii, is capable of infecting almost any nucleated cell of warm-blooded animals, including humans, and establishing tissue cysts that persist throughout the lifetime of the host. Recognition of T. gondii by TLRs is essential for robust IL-12 and IFN-γ production, two major cytokines involved in host resistance to the parasite. In the murine model of infection, robust IL-12 and IFN-γ production have been largely attributed to T. gondii profilin recognition by the TLR11 and TLR12 heterodimer complex, resulting in Myd88-dependent IL-12 production. However, TLR11 or TLR12 deficiency failed to recapitulate the acute susceptibility to T. gondii infection seen in Myd88-/- mice. T. gondii triggers inflammasome activation in a caspase-1-dependent manner resulting in cytokine release; however, it remains undetermined if parasite-mediated inflammasome activation impacts IFN-γ production and host resistance to the parasite. Using mice which lack different inflammasome components, we observed that the inflammasome played a limited role in host resistance when TLR11 remained functional. Strikingly, in the absence of TLR11, caspase-1 and -11 played a significant role for robust CD4+ TH1-derived IFN-γ responses and host survival. Moreover, we demonstrated that in the absence of TLR11, production of the caspase-1-dependent cytokine IL-18 was sufficient and necessary for CD4+ T cell-derived IFN-γ responses. Mechanistically, we established that T. gondii-mediated activation of the inflammasome and IL-18 were critical to maintain robust CD4+ TH1 IFN-γ responses during parasite infection in the absence of TLR11.

Ultrasound pretreatment application in dehydration: its influence on the microstructure, antioxidant activity and carotenoid retention of biofortified Beauregard sweet potato (Ipomoea batatas Lam).

This work aimed to evaluate the effects of ultrasound pretreatment on the microstructure, antioxidant activity, and carotenoid retention of biofortified Beauregard sweet potato (BBSP). The pretreatment was carried out in an ultrasonic bath at 30 °C for 10 min, and it was evaluated in terms of water loss and solid gain. The drying process was performed at two different temperatures (50 and 70 °C). Six different semi-theoretical mathematical models were examined to characterize the drying curves, and quality analyses were executed. The two-terms exponential model provided the best simulation of the drying curves. Drying time was reduced by performing ultrasound pretreatment and by increasing drying temperature. The ultrasound treatment caused greater agglomeration, breakage, or strangulation of the BBSP structure, increasing porosity, and thus increasing drying rates. Drying caused a diminution of total carotenoids content and influenced antioxidant activity. However, the samples pretreated with ultrasound and dried produced lower total carotenoids loss.

COELOMIC TERATOMA IN A BLUE-AND-YELLOW MACAW (ARA ARARAUNA).

A 2-mo-old, female blue-and-yellow macaw (Ara ararauna) presented with severe abdominal distension, pain, and respiratory distress. Ultrasonographic examination detected a heterogeneous mass with multiple anechoic areas, compatible with a multilocular cyst, occupying most of the coelomic cavity. Postmortem examination revealed a mass of 12.0 × 8.5 × 5.0 cm, which had an irregular surface and was connected by a pedicle to the ileum. This mass compressed and displaced the liver, proventriculus, gizzard, and intestines cranially to the left. The cut surface was lobulated, gray-white, mildly firm or soft, and was interspersed with multiple cysts filled with viscous and opaque liquid. Microscopically, it was composed of well- differentiated embryonic tissues from the endoderm, mesoderm, and ectoderm; therefore, it was diagnosed as a mature teratoma, which was theorized to have originated from Meckel's diverticulum. This study is the first, to the authors' knowledge to report a case of a teratoma in a blue-and-yellow macaw.

Behavioural phenotypes predict disease susceptibility and infectiousness.

Behavioural phenotypes may provide a means for identifying individuals that disproportionally contribute to disease spread and epizootic outbreaks. For example, bolder phenotypes may experience greater exposure and susceptibility to pathogenic infection because of distinct interactions with conspecifics and their environment. We tested the value of behavioural phenotypes in larval amphibians for predicting ranavirus transmission in experimental trials. We found that behavioural phenotypes characterized by latency-to-food and swimming profiles were predictive of disease susceptibility and infectiousness defined as the capacity of an infected host to transmit an infection by contacts. While viral shedding rates were positively associated with transmission, we also found an inverse relationship between contacts and infections. Together these results suggest intrinsic traits that influence behaviour and the quantity of pathogens shed during conspecific interactions may be an important contributor to ranavirus transmission. These results suggest that behavioural phenotypes provide a means to identify individuals more likely to spread disease and thus give insights into disease outbreaks that threaten wildlife and humans.

Lymphoid origin of intrinsically activated plasmacytoid dendritic cells in mice.

We identified a novel mouse plasmacytoid dendritic cell (pDC) lineage derived from the common lymphoid progenitors (CLPs) that is dependent on expression of Bcl11a. These CLP-derived pDCs, which we refer to as 'B-pDCs', have a unique gene expression profile that includes hallmark B cell genes, normally not expressed in conventional pDCs. Despite expressing most classical pDC markers such as SIGLEC-H and PDCA1, B-pDCs lack IFN-α secretion, exhibiting a distinct inflammatory profile. Functionally, B-pDCs induce T cell proliferation more robustly than canonical pDCs following Toll-like receptor 9 (TLR9) engagement. B-pDCs, along with another homogeneous subpopulation of myeloid-derived pDCs, display elevated levels of the cell surface receptor tyrosine kinase AXL, mirroring human AXL+ transitional DCs in function and transcriptional profile. Murine B-pDCs therefore represent a phenotypically and functionally distinct CLP-derived DC lineage specialized in T cell activation and previously not described in mice.

Marine mesocosm system: A reliable tool for testing bioaccumulation and effects of seawater enrichment with dissolved iron in reef organisms.

In 2015, a marine mesocosm facility was designed and implemented by the Coral Vivo Project in its research station (Porto Seguro, Bahia State, Brazil) to initially study the effects of global impacts, especially ocean warming and acidification, on coral reefs. However, local impacts, including seawater contamination with metal(loid)s, are considered as a major threat to coral reefs. Also, in 2015, the largest disaster involving a mining dam occurred in Brazil. Iron (Fe) mining tailings originated from the dam failure affected not only freshwater ecosystems (rivers, lakes and lagoons), but also adjacent beaches, mangroves, restingas, reefs and other marine systems. Seawater, sediments and biota were contaminated with metal(loid)s, especially Fe, arsenic (As), mercury (Hg) and manganese (Mn). Therefore, we aimed to adapt the marine mesocosm facility of the Coral Vivo Project to evaluate the bioaccumulation and biological impacts of increasing concentrations of dissolved Fe on a diversity of reef organisms. Results obtained indicate a great versatility and reliability of the marine mesocosm system for application in biological and ecological studies on the isolated effect of seawater dissolved Fe on reef organisms of different functional groups simultaneously.•Studies involving seawater enrichment with dissolved Fe can be performed using a marine mesocosm system.•The marine mesocosm is a reliable tool to study the isolated effects of metal(loid)s on reef organisms.

Mosquito fauna in municipal parks of São Paulo City, Brazil: a preliminary survey.

A mosquito faunal survey was conducted from October 2010 to February 2011 in the municipal parks of São Paulo City, Brazil. A total of 7,015 specimens of 53 taxonomic categories grouped into 12 genera (Aedes, Anopheles, Coquilletidia, Culex, Limatus, Lutzia, Mansonia, Psorophora, Toxorhynchites, Trichoprosopon, Uranotaenia, and Wyeomyia) were collected. The largest and most peripheral parks showed greater species richness compared to smaller and more centralized parks.

Serologic, parasitic, and bacteriologic assessment of captive cracids (Aves: Galliformes: Cracidae) in Brazil.

Captive cracids (Aves: Galliformes: Cracidae), including endangered species, were studied (n = 130) for the assessment of health status, including Aburria jacutinga (black-fronted piping-guan, n = 42), Crax blumenbachii (red-knobbed curassow, n = 54), Craxfasciolata (bare-faced curassow, n = 28), and Penelope obscura (dusky-legged guan, n = 6). The exposure to Mycoplasma gallisepticum (MG), Mycoplasma synoviae (MS), Salmonella pullorum (SP), Salmonella gallinarum (SG), avian paramyxovirus-1 (APMV-1), and infectious bursal disease virus (IBDV) were determined by serology, and SG and SP also were evaluated by culture. Ectoparasites and endoparasites were identified using light microscopy. Sera were negative by the hemagglutination inhibition (HI) test for antibodies to MG or MS, although serum was reactive to MG (32%, 42/130) by the rapid serum agglutination test (SAT). Although positive reactions (26.9%, 35/130) for SP and SG were detected by SAT, cloacal swab cultures were negative for SP and SG. IBDV antibodies were detected by enzyme-linked immunosorbent assay in two dusky-legged guans (1.5%, 2/130). HI antibody titers to APMV-1 were found in 20 (15.3%) cracids, with titers ranging from 16 to 1,024. Fifty percent of birds (65/130) had ectoparasites. Lice (Menacanthus spp.) and mites (Astigmata: Analgesidae, Megninidae; Megninia spp.) were found in red-knobbed curassow; Megninia spp. also were found in bare-faced curassow, black-fronted piping-guan, and dusky-legged guan. Eleven black-fronted piping-guans presented dual parasitism by Megninia spp. and Ornithonyssus spp. Endoparasites were detected in 16.1% (21/130) of birds, and some with multiple parasites. Oocysts of coccidia and eggs of Capillaria spp. (Nematoda: Trichuroidea) were found in the feces of red-knobbed curassow. Eggs of Strongyloides spp. were found in the feces of bare-faced curassow, and eggs of Ascaridia spp., Capillaria spp., and Strongyloides spp. were found in black-fronted piping-guan. Cysts of Blastocystis spp. were found in dusky-legged guan. Antibodies to IBDV and APMV-1 indicate previous exposure. However, considering that birds were clinically normal, immune stimulation might have been from live chicken vaccine strain infections that are widely used in Brazilian poultry. The high parasitism levels indicate that a routine inspection for internal and external parasites is warranted.

Health assessment of captive tinamids (Aves, Tinamiformes) in Brazil.

Ninety-five (95) captive tinamids (Aves, Tinamiformes) of species Crypturellus obsoletus (brown tinamou), Crypturellus parvirostris (small-billed tinamou), Crypturellus tataupa (Tataupa tinamou), Crypturellus undulatus (undulated tinamou), Rhynchotus rufescens (red-winged tinamou), and Tinamus solitarius (solitary tinamou) were evaluated for diseases of mandatory control in the Brazilian Poultry Health Program (PNSA). Antibodies were detected by serum agglutination test (SAT) in 4 birds for Mycoplasma gallisepticum (MG) and in 27 birds for Salmonella Pullorum (SP) and Salmonella Gallinarum (SG). However, by hemagglutination inhibition (HI), sera were negative to MG and Mycoplasma synoviae (MS). Bacteriology was negative for SP and SG. No antibody was detected by HI to avian paramyxovirus type 1. However, antibodies to infectious bursal disease virus were detected in 9.4% (9/95) by ELISA. Fecal parasitology and necropsy revealed Capillaria spp. in 44.2% (42/95), Eimeria rhynchoti in 42.1% (40/95), Strongyloides spp. in 100% (20/20), Ascaridia spp., and unknown sporozoa in small-billed tinamou. Ectoparasites were detected in 42.1% (40/95) by inspection, and collected for identification. The louse Strongylocotes lipogonus (Insecta: Phthiraptera) was found on all Rhynchotus rufescens. An additional four lice species were found on 14 individuals. Traumatic lesions included four individual R. rufescens (4/40, 10%) with rhinotheca fracture, one with mandible fracture and three with posttraumatic ocular lesions (3/40, 7.5%). One C. parvirostris had phalangeal loss, another had tibiotarsal joint ankylosis and another had an open wound on the foot. Results suggest that major poultry infections/ diseases may not be relevant in tinamids, and that this group of birds, as maintained within distances for biosecurity purposes, may not represent a risk to commercial poultry. Ecto- and endoparasites were common, disseminated, and varied; regular monitoring of flocks is recommended for best performance.

Effect of Acupressure on Dental Anxiety in Children: a Pilot Study for a Randomized Clinical Trial.

Background: Anxiety is an important problem in children in dental clinics. Acupressure may be a useful tool to assist in dental procedures in anxious children. Objectives: This pilot study was performed to examine the effects of acupressure on dental anxiety in children undergoing restorative procedures. Methods: Fourteen children aged 7-10 years and with at least one primary molar with caries on the dentine were included in the study. The participants also needed to score at least one point on the modified Venham Picture Test (VPTm) for the determination of anxiety. The children were randomly allocated to two groups: group A - non-documented points for the reduction of anxiety and induction of relaxation; group B - documented points (EX-HN3, Shen Men of auricular acupuncture). The anxiety scale was administered on three occasions: prior to the application of acupressure; immediately after sitting in the dental chair to undergo restorative treatment; and after removal of acupressure at the end of the restorative procedure. Heart rate (HR) was measured when each child sat in the dental chair, after the removal of carious tissue, and after the removal of acupressure. Results: After the procedure, HR (as an indicator of anxiety) was statistically significantly lower in group B than group A (p = 0.02). However, there was no significant difference between the groups regarding anxiety before and during the restorative procedure (VPTm and HR: p > 0.05). Conclusion: The children who received acupressure on documented points for the reduction of anxiety had a significantly lower HR after the restorative procedure. No significant between-group difference was found regarding anxiety measured using a psychometric evaluation (VPTm).

Soil-sediment linkage and trace element contamination in forested/deforested areas of the Itacaiúnas River Watershed, Brazil: To what extent land-use change plays a role?

Trace elements (TE) contamination in forested areas of the Itacaiúnas River Watershed (IRW), Brazilian Amazon, arouses growing interest owing to the rapid deforestation and mining activities. In this study, soils (surface, SS; bottom, BS) and stream sediments (SD) from forested/deforested areas of IRW were analyzed with the aim of (1) evaluating the major sources of TE (mainly As, Ba, Cd, Cu, Co, Cr, Hg, Mo, Mn, Ni, Pb, V, and Zn), and (2) examining the soil-sediment TE link related to land-use change and/or geologic factors. Compositional data analysis (CoDA) was used to eliminate data closure issues and the centred log-ratio (clr) transformation yielded better results in Principal Component Analysis (PCA). The TE distribution pattern was significantly different (p < 0.05) between forested and deforested areas, but in both areas the TE distribution pattern is significantly correlated between SS, BS, and SD, indicating a strong lithogenic control. PCA (clr-transformed) identified the major geochemical bedrock signature as Fe-Ti-V-Cu-Cr-Ni, which is nearly similar in soil and sediments. The more accentuated enrichment and the maximum number of anomalies of these elements were found in the Carajás Basin and are highly coincident with mineral deposits/local lithologies without clear indication of anthropogenic contamination from point sources. Besides geogenic factors, deforestation is also affecting TE distribution in the basin. In deforested areas, Mn was significantly enriched in the surface horizon. Furthermore, linear regression analysis shows stronger TE relationships between soils and sediments in deforested areas than in forested ones, reflecting higher erosion in the former. This could be the reason for the relatively higher enrichment of TE (e.g., Fe, Mn, Cu, Cr, Ni) in deforested sediments. The TE contamination using regional background values provides more accurate results than worldwide reference values. Thus, the former should be considered for a more realistic environmental risk assessment in IRW and other forest ecosystems in the Brazilian Amazon.

IFN-γ mediates Paneth cell death via suppression of mTOR.

Paneth cells constitutively produce antimicrobial peptides and growth factors that allow for intestinal homeostasis, host protection, and intestinal stem cell replication. Paneth cells rely heavily on the glycolytic metabolic program, which is in part controlled by the kinase complex Mechanistic target of rapamycin (mTORC1). Yet, little is known about mTOR importance in Paneth cell integrity under steady-state and inflammatory conditions. Our results demonstrate that IFN-γ, a crucial mediator of the intestinal inflammation, acts directly on murine Paneth cells to alter their mitochondrial integrity and membrane potential, resulting in an TORC1-dependent cell death mechanism distinct from canonical cell death pathways including apoptosis, necroptosis, and pyroptosis. These results were established with the purified cytokine and a physiologically relevant common Th1-inducing human parasite Toxoplasma gondii. Given the crucial role for IFN-γ, which is a cytokine frequently associated with the development of inflammatory bowel disease and compromised Paneth cell functions, the identified mechanisms underlying mTORC1-dependent Paneth cell death downstream of IFN-γ may provide promising novel approaches for treating intestinal inflammation.

Integration of ozonation and an anaerobic expanded granular sludge bed reactor for micropollutant removal from sewage.

Conventional sewage treatment systems are generally not designed to remove micropollutants, requiring the development of new technologies, such as the combination of biological processes with advanced oxidative processes. The configuration of an anaerobic expanded granular sludge bed (EGSB) reactor stands out for its use of granular biomass and high sludge bed expansion. Ozonation is an advanced oxidative process that stands out as one of the most promising technologies for the degradation of micropollutants. Thus, the present work aimed to evaluate the removal of drugs through the application of ozonation as a polishing process for the effluent of an EGSB reactor that was fed with synthetic sewage. Ozonation was shown to be efficient in the degradation of these compounds, reaching removals above 90%. It was found that the degradation profile of each drug varied according to its chemical structure since some drugs are more susceptible to oxidation than others and since the concentrations of pharmaceuticals are also related to their removal. Moreover, the assessment of risks to the environment and human health confirmed the need to assess the best scenario for risk reduction considering all drugs, since even with almost complete removal of some compounds, the effluents still showed toxicity. Thus, the high removal efficiencies found for the evaluated micropollutants showed that this technique has the potential to be used to improve the quality of biological reactor effluents or even to be combined in effluent reuse systems.

[Analysis of production, impact, and collaboration networks in scientific research in Scopus for Peru from 2000 to 2019]. / Análisis de producción, impacto y redes de colaboración en investigaciones científicas en Scopus en Perú de 2000 a 2019.

INTRODUCTION: Peru is a developing country with increasing scientific production. However, it is necessary to understand the trends, impact, and collaborative networks of research to plan for policy improvements. OBJECTIVE: We analyzed the production, impact, and collaboration networks in the Peruvian scientific production between 2000 and 2019. METHODS: We did an observational analytical study. We searched Scopus for all the publications with at least one author with a Peruvian affiliation declared in the author byline. A descriptive analysis of the different characteristics, trends, and scientific collaboration was carried out. Collaboration networks were plotted using VOSviewer. RESULTS: Between 2000 and 2019, Peru had a total of 24 482 publications in scientific journals, with an average annual growth of 13.6%. Of the total, 70% of all the articles were cataloged as Clinical Medicine and Biomedical Sciences. Only half of the articles had a Peruvian affiliation. The countries with the largest share of collaboration were the United States and Brazil, and the articles with international collaboration had the highest number of citations per publication. CONCLUSIONS: Scientific production in Peru has increased in recent years, with a significant percentage of publications based on international collaboration and led by authors with non-Peruvian affiliations. It is necessary to strengthen collaboration ties between Peruvian and foreign institutions. Furthermore, it is essential to propitiate further research that will help solve the country's problems.

INTRODUCCIÓN: Perú es un país en vías de desarrollo, con una producción científica en aumento. Sin embargo, es necesario entender las tendencias, el impacto y la colaboración de sus investigaciones para promover una mejora continua de las mismas. OBJETIVO: Buscamos analizar la producción, el impacto y las redes de colaboración en la producción científica peruana entre los años 2000 y 2019. MÉTODOS: Realizamos un estudio analítico observacional haciendo una búsqueda en Scopus de todas las publicaciones que hayan tenido al menos un autor peruano en su filiación. Sobre eso, realizamos un análisis descriptivo de las diferentes características, tendencias y tipo de colaboración científica. Graficamos las redes de colaboración mediante VOSviewer. RESULTADOS: Entre los años 2000 y 2019, Perú tuvo un total de 24 482 publicaciones en revistas científicas, con un crecimiento anual promedio de 13,6%. Del total de artículos científicos, 70% de todas las publicaciones pertenecieron a las áreas de medicina clínica y ciencias biomédicas. Solo la mitad de los artículos contaban con filiación peruana. Los países con mayor colaboración fueron Estados Unidos y Brasil, y los artículos con colaboración internacional tuvieron mayor cantidad de citas por publicación. CONCLUSIONES: En años recientes, ha habido un incremento de la producción científica en Perú, con un gran porcentaje de publicaciones basadas en la colaboración internacional y lideradas por autores con filiación no peruana. Es necesario fortalecer lazos de colaboración entre instituciones peruanas y extranjeras. Además, es fundamental el incitar un mayor liderazgo en investigaciones que solucionen problemas del país.

Occupational stress of nurses from the Mobile Emergency Care Service.

OBJECTIVE: To evaluate stress, and to associate it with sociodemographic and clinical aspects of nurses from the Mobile Emergency Care Service. METHOD: This is an observational, cross-sectional and quantitative study conducted with 123 nurses, who answered a questionnaire to assess sociodemographic and clinical variables, and the Job Stress Scale, which evaluates stress in the workplace. RESULTS: The results indicated that most of them were women, 20 to 40 years old, married, without another employment bond and with specialization course. They had low control and low demand at work and performed a passive work. Women reported passive work and high stress levels, while men were equally divided in active and passive work with low stress levels. CONCLUSION: Passive work is harmful to health and it is related to lack of autonomy, decision-making, and social support. It may lead to reduced ability to solve problems faced in daily work routine.

T-bet-independent Th1 response induces intestinal immunopathology during Toxoplasma gondii infection.

Coordinated production of IFN-γ by innate and adaptive immune cells is central for host defense, but can also trigger immunopathology. The investigation of the lymphoid cell-specific contribution to the IFN-γ-mediated intestinal pathology during Toxoplasma gondii infection identified CD4+ T cells as a key cell population responsible for IFN-γ-dependent intestinal inflammation and Paneth cell loss, where T-bet-dependent group 1 innate lymphoid cells have a minor role in driving the parasite-induced immunopathology. This was evident from the analysis of T-bet deficiency that did not prevent the intestinal inflammation and instead revealed that T-bet-deficient CD4+ Th1 cells are sufficient for T. gondii-triggered acute ileitis and Paneth cell loss. These results revealed that T-bet-independent Th1 effector cells are major functional mediators of the type I immunopathological response during acute gastrointestinal infection.

Loss of Paneth Cell Autophagy Causes Acute Susceptibility to Toxoplasma gondii-Mediated Inflammation.

The protozoan parasite Toxoplasma gondii triggers severe small intestinal immunopathology characterized by IFN-γ- and intestinal microbiota-mediated inflammation, Paneth cell loss, and bacterial dysbiosis. Paneth cells are a prominent secretory epithelial cell type that resides at the base of intestinal crypts and releases antimicrobial peptides. We demonstrate that the microbiota triggers basal Paneth cell-specific autophagy via induction of IFN-γ, a known trigger of autophagy, to maintain intestinal homeostasis. Deletion of the autophagy protein Atg5 specifically in Paneth cells results in exaggerated intestinal inflammation characterized by complete destruction of the intestinal crypts resembling that seen in pan-epithelial Atg5-deficient mice. Additionally, lack of functional autophagy in Paneth cells within intestinal organoids and T. gondii-infected mice causes increased sensitivity to the proinflammatory cytokine TNF along with increased intestinal permeability, leading to exaggerated microbiota- and IFN-γ-dependent intestinal immunopathology. Thus, Atg5 expression in Paneth cells is essential for tissue protection against cytokine-mediated immunopathology during acute gastrointestinal infection.

Detection of Culex flavivirus and Aedes flavivirus nucleotide sequences in mosquitoes from parks in the city of São Paulo, Brazil.

The dengue viruses are widespread in Brazil and are a major public health concern. Other flaviviruses also cause diseases in humans, although on a smaller scale. The city of São Paulo is in a highly urbanized area with few green spaces apart from its parks, which are used for recreation and where potential vertebrate hosts and mosquito vectors of pathogenic Flavivirus species can be found. Although this scenario can contribute to the transmission of Flavivirus to humans, little is known about the circulation of members of this genus in these areas. In light of this, the present study sought to identify Flavivirus infection in mosquitoes (Diptera: Culicidae) collected in parks in the city of São Paulo. Seven parks in different sectors of the city were selected. Monthly mosquito collections were carried out in each park from March 2011 to February 2012 using aspiration and traps (Shannon and CD C-CO2). Nucleic acids were extracted from the mosquitoes collected and used for reverse-transcriptase and real-time polymerase chain reactions with genus-specific primers targeting a 200-nucleotide region in the Flavivirus NS5 gene. Positive samples were sequenced, and phylogenetic analyses were performed. Culex and Aedes were the most frequent genera of Culicidae collected. Culex flavivirus (CxFV)-related and Aedes flavivirus (AEFV)- related nucleotide sequences were detected in 17 pools of Culex and two pools of Aedes mosquitoes, respectively, among the 818 pools of non-engorged females analyzed. To the best of our knowledge, this is the first report of CxFV and AEFV in the city of São Paulo and Latin America, respectively. Both viruses are insect- specific flaviviruses, a group known to replicate only in mosquito cells and induce a cytopathic effect in some situations. Hence, our data suggests that CxFV and AEFV are present in Culex and Aedes mosquitoes, respectively, in parks in the city of São Paulo. Even though Flavivirus species of medical importance were not detected, surveillance is recommended in the study areas because of the presence of vertebrates and mosquitoes that could act as amplifying hosts and vectors of flaviviruses, providing the required conditions for circulation of these viruses.