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

Endotoxin exposure during sensitization to Blomia tropicalis allergens shifts TH2 immunity towards a TH17-mediated airway neutrophilic inflammation: role of TLR4 and TLR2

Experimental evidence and epidemiological studies indicate that exposure to endotoxin lipopolysaccharide (eLPS) or other TLR agonists prevent asthma. We have previously shown in the OVA-model of asthma that eLPS administration during alum-based allergen sensitization blocked the development of lung TH2 immune responses via MyD88 pathway and IL-12/IFN-γ axis. In the present work we determined the effect of eLPS exposure during sensitization to a natural airborne allergen extract derived from the house dust mite Blomia tropicalis (Bt). Mice were subcutaneously sensitized with Bt allergens co-adsorbed onto alum with or without eLPS and challenged twice intranasally with Bt. Cellular and molecular parameters of allergic lung inflammation were evaluated 24 h after the last Bt challenge. Exposure to eLPS but not to ultrapure LPS (upLPS) preparation during sensitization to Bt allergens decreased the influx of eosinophils and increased the influx of neutrophils to the airways. Inhibition of airway eosinophilia was not observed in IFN-γdeficient mice while airway neutrophilia was not observed in IL-17RA-deficient mice as well in mice lacking MyD88, CD14, TLR4 and, surprisingly, TLR2 molecules. Notably, exposure to a synthetic TLR2 agonist (PamCSK4) also induced airway neutrophilia that was dependent on TLR2 and TLR4 molecules. In the OVA model, exposure to eLPS or PamCSK4 suppressed OVA-induced airway inflammation. Our results suggest that B. tropicalis allergens engage TLR4 that potentiates TLR2 signaling. This dual TLR activation during sensitization results in airway neutrophilic inflammation associated with increased frequency of lung TH17 cells. Our work highlight the complex interplay between bacterial products, house dust mite allergens and TLR signaling in the induction of different phenotypes of airway inflammation.State of Sao Paulo Foundation for Research Support (FAPESP - 07/03031-3)State of Sao Paulo Foundation for Research Support (FAPESP - 11/17880-8)CAPES, Brazilian Council of Scientific and Technologic Developmen

Impact of a Citywide Sanitation Program in Northeast Brazil on Intestinal Parasites Infection in Young Children

BACKGROUND: Sanitation affects health, especially that of young children. Residents of Salvador, in Northeast Brazil, have had a high prevalence of intestinal parasites. A citywide sanitation intervention started in 1996 aimed to raise the level of sewer coverage from 26% to 80% of households. OBJECTIVES: We evaluated the impact of this intervention on the prevalence of Ascaris lumbricoides, Trichuris trichuria, and Giardia duodenalis infections in preschool children. METHODS: The evaluation was composed of two cross-sectional studies (1998 and 2003-2004), each of a sample of 681 and 976 children 1-4 years of age, respectively. Children were sampled from 24 sentinel areas chosen to represent the range of environmental conditions in the study site. Data were collected using an individual/household questionnaire, and an environmental survey was conducted in each area before and after the intervention to assess basic household and neighborhood sanitation conditions. Stool samples were examined for the presence of intestinal parasites. The effect of the intervention was estimated by hierarchical modeling, fitting a sequence of multivariate regression models. FINDINGS: The prevalence ofA. lumbricoides infection was reduced from 24.4% to 12.0%, T. trichuria from 18.0% to 5.0%, and G. duodenalis from 14.1% to 5.3%. Most of this reduction appeared to be explained by the increased coverage in each neighborhood by the sewage system constructed during the intervention. The key explanatory variable was thus an ecological measure of exposure and not household-based, suggesting that the parasite transmission prevented by the program was mainly in the public (vs. the domestic) domain. CONCLUSION: This study, using advanced statistical modeling to control for individual and ecological potential confounders, demonstrates the impact on intestinal parasites of sanitation improvements implemented at the scale of a large population

Circulating trans-sialidase activity and trans-sialidase-inhibiting antibodies in Trypanosoma cruzi-infected mice.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-09-09T16:46:16Z No. of bitstreams: 1 Alcantara N NM Circulating....pdf: 764426 bytes, checksum: 5944d5474da91486002043b53a0614d4 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2014-09-09T16:46:35Z (GMT) No. of bitstreams: 1 Alcantara N NM Circulating....pdf: 764426 bytes, checksum: 5944d5474da91486002043b53a0614d4 (MD5)Made available in DSpace on 2014-09-09T16:56:31Z (GMT). No. of bitstreams: 1 Alcantara N NM Circulating....pdf: 764426 bytes, checksum: 5944d5474da91486002043b53a0614d4 (MD5) Previous issue date: 1995Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laborat6rio de Imunologia Molecular e Celular. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório Avançado de Saúde Púbica. Salvador, BA, BrasilParasite-derived trans-sialidase (TS) activity was demonstrated in the serum and blood of Trypanosoma cruzi-infected mice. Serum TS activity levels correlated well with parasitemia in BALB/c and Swiss mice during the initial stages of the infection. However, in later stages the TS activity levels decreased despite increasing parasitemia. This coincided with the appearance of circulating TS antibodies. On the other hand, there was always a good correlation between TS activity and parasitemia in athymic nude mice. Sera from mice with high parasitemia and low TS activity inhibited TS activity in vitro. The inhibition was also observed with purified serum IgG, and it was absorbed by staphylococcal protein A, indicating that it was caused by anti-TS IgG antibodies. These antibodies inhibited the enzymatic activity of insolubilized TS, indicating that they act by interfering with the catalytic site rather than by aggregating the enzyme. The presence of inhibitory antibodies, however, did not prevent the progression of parasitemia in BALB/c mice

Otimização da recuperação de larvas filarioides de S. Stercoralis para obtenção de antígenos

O diagnóstico definitivo da estrongiloidíase é realizado pela pesquisa de larvas nas fezes, utilizando-se principalmente o método de Baermann-Moraes, apesar da cultura em placa de ágar (CPA) apresentar maior sensibilidade. Além da finalidade diagnóstica, a CPA pode ser utilizada no cultivo das larvas de Strongyloides stercoralis para a produção de antígenos. Entretanto, as fezes têm muito detritos de alimentos e bactérias, o que prejudica a separação das larvas em uma suspensão limpa. O objetivo deste trabalho foi aperfeiçoar o protocolo da recuperação das larvas filarioides de S. stercoralis das culturas em placas de ágar, comparando três métodos: (a) a lavagem das superfícies das placas de ágar com tampão fosfato-salina e (b) o método de Baermann-Moraes de todo o material contido nas placas (fezes e ágar) ou (c) somente com as fezes retiradas das placas, após o período de incubação das culturas. Além disso, foi avaliada a recuperação de larvas filariodes de culturas contendo estreptomicina e anfotericina. O procedimento de lavagem manual das superfícies das placas recuperou um número maior de larvas, quando comparado com os outros dois métodos (

Otimização da recuperação de larvas filarioides de S. Stercoralis para obtenção de antígenos

O diagnóstico definitivo da estrongiloidíase é realizado pela pesquisa de larvas nas fezes, utilizando-se principalmente o método de Baermann-Moraes, apesar da cultura em placa de ágar (CPA) apresentar maior sensibilidade. Além da finalidade diagnóstica, a CPA pode ser utilizada no cultivo das larvas de Strongyloides stercoralis para a produção de antígenos. Entretanto, as fezes têm muito detritos de alimentos e bactérias, o que prejudica a separação das larvas em uma suspensão limpa. O objetivo deste trabalho foi aperfeiçoar o protocolo da recuperação das larvas filarioides de S. stercoralis das culturas em placas de ágar, comparando três métodos: (a) a lavagem das superfícies das placas de ágar com tampão fosfato-salina e (b) o método de Baermann-Moraes de todo o material contido nas placas (fezes e ágar) ou (c) somente com as fezes retiradas das placas, após o período de incubação das culturas. Além disso, foi avaliada a recuperação de larvas filariodes de culturas contendo estreptomicina e anfotericina. O procedimento de lavagem manual das superfícies das placas recuperou um número maior de larvas, quando comparado com os outros dois métodos (