Spontaneous cytokine production in children according to biological characteristics and environmental exposures.

BACKGROUND: Environmental factors are likely to have profound effects on the development of host immune responses, with serious implications for infectious diseases and inflammatory disorders such as asthma. OBJECTIVE: This study was designed to investigate the effects of environmental exposures on the cytokine profile of children. METHODS: The study involved measurement of T helper (Th) 1 (interferon-gamma), 2 [interleukin (IL)-5 and IL-13], and the regulatory cytokine IL-10 in unstimulated peripheral blood leukocytes from 1,376 children 4-11 years of age living in a poor urban area of the tropics. We also assessed the impact of environmental exposures in addition to biological characteristics recorded at the time of blood collection and earlier in childhood (0-3 years before blood collection). RESULTS: The proportion of children producing IL-10 was greater among those without access to drinking water [p < 0.05, chi-square test, odds ratio (OR) = 1.67]. The proportion of children producing IL-5 and IL-10 (OR = 10.76) was significantly greater in households that had never had a sewage system (p < 0.05, trend test). CONCLUSIONS: These data provide evidence for the profound effects of environmental exposures in early life as well as immune homeostasis in later childhood. Decreased hygiene (lack of access to clean drinking water and sanitation) in the first 3 years of life is associated with higher spontaneous IL-10 production up to 8 years later in life

Composition and phenology of herbaceous species in heterogeneous reforestation

Heterogeneous reforestations are constituted mainly by plant species with easy germination, fast growing, and which follows the Resolução SMA 8/07. Due to the scarcity of information about the herbaceous component in heterogeneous reforestations, the present study aimed to verify the presence of cerrado (savannah) herbaceous species in a heterogeneous reforestation in São Carlos, São Paulo State, twenty five species belonging to seven families were found, in the heterogeneous reforestation whereas in the cerrado, 35 herbaceous species belonging to nine families were registered. Seventeen cerrado species were also found at the reforestation area. Cerrado species flowering was positively correlated to the average temperature and to pluvial precipitation. In reforestation, flowering was not correlated to climatic variables. In conclusion, the heterogeneous reforestation area sheltered the major number of cerrado herbaceous species, but long-term studies are still needed to a better comprehension of the flowering dynamics of herbaceous plants in heterogeneous reforestation areas.Os reflorestamentos heterogêneos normalmente são feitos utilizando-se espécies vegetais de fácil germinação, rápido crescimento e que atendam à Resolução SMA 8/07. Tendo em vista serem escassas as informações sobre o componente herbáceo em reflorestamentos heterogêneos, o presente estudo teve por objetivo verificar a presença de plantas herbáceas de cerrado em um reflorestamento heterogêneo em São Carlos, estado de São Paulo. Foram levantadas as espécies herbáceas presentes em transectos estabelecidos em área de reflorestamento heterogêneo e em área próxima de cerrado stricto sensu. No reflorestamento heterogêneo foram registradas 25 espécies, pertencentes a sete famílias, e no cerrado foram registradas 35 espécies herbáceas, pertencentes a nove famílias. Dezessete espécies do cerrado também foram encontradas no reflorestamento. A floração das espécies de cerrado correlacionou-se positivamente com a temperatura média e a precipitação pluvial. No reflorestamento heterogêneo não foi encontrada correlação entre floração e variáveis meteorológicas. Conclui-se que a área de reflorestamento heterogêneo abriga grande parte da flora herbácea existente no cerrado da região, porém investigações de longo prazo ainda são necessárias para a compreensão adequada da dinâmica das plantas herbáceas em áreas de reflorestamento heterogêneo

Genetic and virulence characterization of colistin-resistant and colistin-sensitive A. baumannii clinical isolates.

Treatment of infections caused by A. baumannii is becoming a challenge due to the ability to develop multidrug-resistance, virulence, and high mortality. We described the colistin resistance and virulence genes present in sixA. baumannii clinical isolates using WGS, expression by qPCR, and virulence in the Galleria mellonella model. The colistin-resistant isolates were assigned as ST233 and the colistin-susceptible isolates as ST236 and ST407. The colistin-resistant isolates contained mutations within PmrA/PmrB, and the pmrA showed up-regulation in all of them. Only one colistin-resistant isolate indicating virulence in G. mellonella. This particular isolate belonged to a different clone, and it was the only isolate that presented non-synonymous mutations in pmrB. Colistinresistance in A. baumannii isolates seems to be caused by up-regulation of pmrA gene. Only one isolate appeared to be virulent in the G. mellonella model. This finding indicating low virulence in isolates belonging to emerging clones circulating in our hospital

Biogeographical ancestry is associated with socioenvironmental conditions and infections in a Latin American urban population.

Racial inequalities are observed for different diseases and are mainly caused by differences in socioeconomic status between ethnoracial groups. Genetic factors have also been implicated, and recently, several studies have investigated the association between biogeographical ancestry (BGA) and complex diseases. However, the role of BGA as a proxy for non-genetic health determinants has been little investigated. Similarly, studies comparing the association of BGA and self-reported skin colour with these determinants are scarce. Here, we report the association of BGA and self-reported skin colour with socioenvironmental conditions and infections. We studied 1246 children living in a Brazilian urban poor area. The BGA was estimated using 370,539 genome-wide autosomal markers. Standardised questionnaires were administered to the children's guardians to evaluate socioenvironmental conditions. Infection (or pathogen exposure) was defined by the presence of positive serologic test results for IgG to seven pathogens (Toxocara spp, Toxoplasma gondii, Helicobacter pylori, and hepatitis A, herpes simplex, herpes zoster and Epstein-Barr viruses) and the presence of intestinal helminth eggs in stool samples (Ascaris lumbricoides and Trichiuris trichiura). African ancestry was negatively associated with maternal education and household income and positively associated with infections and variables, indicating poorer housing and living conditions. The self-reported skin colour was associated with infections only. In stratified analyses, the proportion of African ancestry was associated with most of the outcomes investigated, particularly among admixed individuals. In conclusion, BGA was associated with socioenvironmental conditions and infections even in a low-income and highly admixed population, capturing differences that self-reported skin colour miss. Importantly, our findings suggest caution in interpreting significant associations between BGA and diseases as indicative of the genetic factors involved

Respiratory allergy to Blomia tropicalis: Immune response in four syngeneic mouse strains and assessment of a low allergen-dose, short-term experimental model

<p>Abstract</p> <p>Background</p> <p>The dust mite <it>Blomia tropicalis </it>is an important source of aeroallergens in tropical areas. Although a mouse model for <it>B. tropicalis </it>extract (<it>Bt</it>E)-induced asthma has been described, no study comparing different mouse strains in this asthma model has been reported. The relevance and reproducibility of experimental animal models of allergy depends on the genetic background of the animal, the molecular composition of the allergen and the experimental protocol.</p> <p>Objectives</p> <p>This work had two objectives. The first was to study the anti-<it>B. tropicalis </it>allergic responses in different mouse strains using a short-term model of respiratory allergy to <it>Bt</it>E. This study included the comparison of the allergic responses elicited by <it>Bt</it>E with those elicited by ovalbumin in mice of the strain that responded better to <it>Bt</it>E sensitization. The second objective was to investigate whether the best responder mouse strain could be used in an experimental model of allergy employing relatively low <it>Bt</it>E doses.</p> <p>Methods</p> <p>Groups of mice of four different syngeneic strains were sensitized subcutaneously with 100 μg of <it>Bt</it>E on days 0 and 7 and challenged four times intranasally, at days 8, 10, 12, and 14, with 10 μg of <it>Bt</it>E. A/J mice, that were the best responders to <it>Bt</it>E sensitization, were used to compare the <it>B. tropicalis</it>-specific asthma experimental model with the conventional experimental model of ovalbumin (OVA)-specific asthma. A/J mice were also sensitized with a lower dose of <it>Bt</it>E.</p> <p>Results</p> <p>Mice of all strains had lung inflammatory-cell infiltration and increased levels of anti-<it>Bt</it>E IgE antibodies, but these responses were significantly more intense in A/J mice than in CBA/J, BALB/c or C57BL/6J mice. Immunization of A/J mice with <it>Bt</it>E induced a more intense airway eosinophil influx, higher levels of total IgE, similar airway hyperreactivity to methacholine but less intense mucous production, and lower levels of specific IgE, IgG1 and IgG2 antibodies than sensitization with OVA. Finally, immunization with a relatively low <it>Bt</it>E dose (10 μg per subcutaneous injection per mouse) was able to sensitize A/J mice, which were the best responders to high-dose <it>Bt</it>E immunization, for the development of allergy-associated immune and lung inflammatory responses.</p> <p>Conclusions</p> <p>The described short-term model of <it>Bt</it>E-induced allergic lung disease is reproducible in different syngeneic mouse strains, and mice of the A/J strain was the most responsive to it. In addition, it was shown that OVA and <it>Bt</it>E induce quantitatively different immune responses in A/J mice and that the experimental model can be set up with low amounts of <it>Bt</it>E.</p

Toxocara Seropositivity, Atopy and Wheezing in Children Living in Poor Neighbourhoods in Urban Latin American

Background Toxocara canis and T. cati are parasites of dogs and cats, respectively, that infect humans and cause human toxocariasis. Infection may cause asthma-like symptoms but is often asymptomatic and is associated with a marked eosinophilia. Previous epidemiological studies indicate that T. canis infection may be associated with the development of atopy and asthma. Objectives To investigate possible associations between Toxocara spp. seropositivity and atopy and childhood wheezing in a population of children living in non-affluent areas of a large Latin American city. Methods The study was conducted in the city of Salvador, Brazil. Data on wheezing symptoms were collected by questionnaire, and atopy was measured by the presence of aeroallergen-specific IgE (sIgE). Skin prick test (SPT), total IgE and peripheral eosinophilia were measured. Toxocara seropositivity was determined by the presence of anti-Toxocara IgG antibodies, and intestinal helminth infections were determined by stool microscopy. Findings Children aged 4 to 11 years were studied, of whom 47% were seropositive for anti-Toxocara IgG; eosinophilia >4% occurred in 74.2% and >10% in 25.4%; 59.6% had elevated levels of total IgE; 36.8% had sIgE≥0.70 kU/L and 30.4% had SPT for at least one aeroallergen; 22.4% had current wheezing symptoms. Anti-Toxocara IgG was positively associated with elevated eosinophils counts, total IgE and the presence of specific IgE to aeroallergens but was inversely associated with skin prick test reactivity. Conclusion The prevalence of Toxocara seropositivity was high in the studied population of children living in conditions of poverty in urban Brazil. Toxocara infection, although associated with total IgE, sIgE and eosinophilia, may prevent the development of skin hypersensitivity to aeroallergens, possibly through increased polyclonal IgE and the induction of a modified Th2 immune reaction

Applied immuno-epidemiological research: an approach for integrating existing knowledge into the statistical analysis of multiple immune markers.

BACKGROUND: Immunologists often measure several correlated immunological markers, such as concentrations of different cytokines produced by different immune cells and/or measured under different conditions, to draw insights from complex immunological mechanisms. Although there have been recent methodological efforts to improve the statistical analysis of immunological data, a framework is still needed for the simultaneous analysis of multiple, often correlated, immune markers. This framework would allow the immunologists' hypotheses about the underlying biological mechanisms to be integrated. RESULTS: We present an analytical approach for statistical analysis of correlated immune markers, such as those commonly collected in modern immuno-epidemiological studies. We demonstrate i) how to deal with interdependencies among multiple measurements of the same immune marker, ii) how to analyse association patterns among different markers, iii) how to aggregate different measures and/or markers to immunological summary scores, iv) how to model the inter-relationships among these scores, and v) how to use these scores in epidemiological association analyses. We illustrate the application of our approach to multiple cytokine measurements from 818 children enrolled in a large immuno-epidemiological study (SCAALA Salvador), which aimed to quantify the major immunological mechanisms underlying atopic diseases or asthma. We demonstrate how to aggregate systematically the information captured in multiple cytokine measurements to immunological summary scores aimed at reflecting the presumed underlying immunological mechanisms (Th1/Th2 balance and immune regulatory network). We show how these aggregated immune scores can be used as predictors in regression models with outcomes of immunological studies (e.g. specific IgE) and compare the results to those obtained by a traditional multivariate regression approach. CONCLUSION: The proposed analytical approach may be especially useful to quantify complex immune responses in immuno-epidemiological studies, where investigators examine the relationship among epidemiological patterns, immune response, and disease outcomes

Sarcoma de Kaposi: Uma Análise Abrangente dos Aspectos Dermatológicos e Oncologicos

Kaposi's Sarcoma (KS) is a type of cancer originating in the cells of blood and lymphatic vessels, closely associated with human herpes virus type 8 (HHV-8). The epidemiology of KS varies significantly around the world, with a notably high prevalence in sub-Saharan Africa, where it is often linked to AIDS and found endemically in children and the elderly. In sub-Saharan Africa, the prevalence of HHV-8 is high, and transmission occurs both from mother to child and between adults. The introduction of Antiretroviral Therapy (ART) has reduced the incidence of KS in HIV-positive patients, but KS remains common in South African children. Clinically, KS presents with pinkish-purple spots on the skin, and can also affect mucous membranes and internal organs. The primary phase of HHV-8 infection is generally asymptomatic but can lead to severe symptoms in immunocompromised individuals. The diagnosis is confirmed through histopathology, identifying spindle cells and the presence of the HHV-8 LANA antigen. Clinically, KS presents with pinkish-purple spots on the skin, and can also affect mucous membranes and internal organs. The primary phase of HHV-8 infection is generally asymptomatic but can lead to severe symptoms in immunocompromised individuals. The diagnosis is confirmed through histopathology, identifying spindle cells and the presence of the HHV-8 LANA antigen.El Sarcoma de Kaposi (SK) es un tipo de cáncer que se origina en las células de los vasos sanguíneos y linfáticos, estrechamente asociado con el virus del herpes humano tipo 8 (HHV-8). La epidemiología del SK varía significativamente en todo el mundo, con una prevalencia notablemente alta en el África subsahariana, donde a menudo se vincula con el SIDA y se presenta endémicamente en niños y ancianos. En el África subsahariana, la prevalencia del HHV-8 es alta y la transmisión se produce tanto de madre a hijo como entre adultos. La introducción de la terapia antirretroviral (TAR) ha reducido la incidencia de SK en pacientes VIH positivos, pero el SK sigue siendo común en los niños sudafricanos. Clínicamente, el SK se presenta con manchas de color rosado violáceo en la piel y también puede afectar las membranas mucosas y los órganos internos. La fase primaria de la infección por HHV-8 generalmente es asintomática, pero puede provocar síntomas graves en personas inmunodeprimidas. El diagnóstico se confirma mediante histopatología, identificando células fusiformes y la presencia del antígeno LANA HHV-8. Clínicamente, el SK se presenta con manchas de color rosado violáceo en la piel y también puede afectar las membranas mucosas y los órganos internos. La fase primaria de la infección por HHV-8 generalmente es asintomática, pero puede provocar síntomas graves en personas inmunodeprimidas. El diagnóstico se confirma mediante histopatología, identificando células fusiformes y la presencia del antígeno LANA HHV-8.O Sarcoma de Kaposi (SK) é um tipo de câncer originado nas células dos vasos sanguíneos e linfáticos, estreitamente associado ao vírus herpes humano tipo 8 (HHV-8). A epidemiologia do SK varia significativamente pelo mundo, com uma prevalência notavelmente alta na África Subsaariana, onde é frequentemente relacionado à AIDS e encontrado endemicamente em crianças e idosos. Na África Subsaariana, a prevalência de HHV-8 é alta, e a transmissão ocorre tanto de mãe para filho quanto entre adultos. A introdução da Terapia Antirretroviral (TARV) reduziu a incidência de SK em pacientes HIV positivos, mas o SK permanece comum em crianças sul-africanas. Clinicamente, o SK apresenta-se com manchas rosa-púrpura na pele, podendo também afetar mucosas e órgãos internos. A fase primária da infecção pelo HHV-8 é geralmente assintomática, mas pode levar a sintomas graves em indivíduos imunocomprometidos. O diagnóstico é confirmado por meio de histopatologia, identificando células fusiformes e a presença do antígeno LANA do HHV-8. Clinicamente, o SK apresenta-se com manchas rosa-púrpura na pele, podendo também afetar mucosas e órgãos internos. A fase primária da infecção pelo HHV-8 é geralmente assintomática, mas pode levar a sintomas graves em indivíduos imunocomprometidos. O diagnóstico é confirmado por meio de histopatologia, identificando células fusiformes e a presença do antígeno LANA do HHV-8

Dissociation between skin test reactivity and anti-aeroallergen IgE: Determinants among urban Brazilian children.

BACKGROUND: The dissociation between specific IgE and skin prick test reactivity to aeroallergens, a common finding in populations living in low and middle-income countries, has important implications for the diagnosis and treatment of allergic diseases. Few studies have investigated the determinants of this dissociation. In the present study, we explored potential factors explaining this dissociation in children living in an urban area of Northeast Brazil, focusing in particular on factors associated with poor hygiene. METHODS: Of 1445 children from low income communities, investigated for risk factors of allergies, we studied 481 with specific IgE antibodies to any of Blomia tropicalis, Dermatophagoides pteronyssinus, Periplaneta americana and Blatella germanica allergens. Data on demographic, environmental and social exposures were collected by questionnaire; serum IgG and stool examinations were done to detect current or past infections with viral, bacterial, protozoan and intestinal helminth pathogens. We measured atopy by skin prick testing (SPT) and specific IgE (sIgE) to aerollergens in serum (by ImmunoCAP). SIgE reactivity to B. tropicalis extract depleted of carbohydrates was measured by an in-house ELISA. Total IgE was measured by in house capture ELISA. SNPs were typed using Illumina Omni 2.5. RESULTS: Negative skin prick tests in the presence of specific IgE antibodies were frequent. Factors independently associated with a reduced frequency of positive skin prick tests were large number of siblings, the presence of IgG to herpes simplex virus, Ascaris lumbricoides and Trichuris trichiura infections, living in neighborhoods with infrequent garbage collection, presence of rodents and cats in the household and sIgE reactivity to glycosylated B. tropicalis allergens. Also, SNP on IGHE (rs61737468) was negatively associated with SPT reactivity. CONCLUSIONS: A variety of factors were found to be associated with decreased frequency of SPT such as unhygienic living conditions, infections, total IgE, IgE response to glycosylated allergens and genetic polymorphisms, indicating that multiple mechanisms may be involved. Our data, showing that exposures to an unhygienic environment and childhood infections modulate immediate allergen skin test reactivity, provide support for the "hygiene hypothesis"