Coassociations between IL10 polymorphisms, IL-10 production, helminth infection, and asthma/wheeze in an urban tropical population in Brazil.

BACKGROUND: Helminth infections are associated with protection against allergies. It is postulated that IL-10 production after helminth infection suppresses skin hypersensitivity and increases IgG4 production, protecting against allergies. OBJECTIVE: We aimed to determine whether IL10 polymorphisms are associated with helminth infection and the risk of wheeze and allergy. METHODS: Twelve IL10 single nucleotide polymorphisms were genotyped in 1353 children aged 4 to 11 years living in a poor urban area in Salvador, Brazil. Wheezing status, Ascaris lumbricoides and Trichuris trichiura infection, IL-10 production by peripheral blood leukocytes stimulated with A lumbricoides extract, serum total IgE levels, specific IgE levels, skin prick test responses to common aeroallergens, and IgG4 and IgE anti-A lumbricoides antibody levels were measured in all children. Association tests were performed by using logistic or linear regression when appropriate, including sex, age, helminth infection, and principal components for ancestry informative markers as covariates by using PLINK. RESULTS: Allele G of marker rs3024496 was associated with the decreased production of IL-10 by peripheral blood leukocytes in response to A lumbricoides stimulation. Allele C of marker rs3024498 was negatively associated with helminth infection or its markers. Marker rs3024492 was positively associated with the risk of atopic wheeze, total IgE levels, and skin prick test responses to cockroach. CONCLUSIONS: Our findings suggest that IL10 polymorphisms might play a role in the production of IL-10, helminth infection, and allergy. We hypothesize that polymorphisms related to protection against helminths, which would offer an evolutionary advantage to subjects in the past, might be associated with increased risk of allergic diseases.

The effect of single and multiple infections on atopy and wheezing in children.

BACKGROUND: The current epidemic of asthma and atopy has been explained by alterations in immune responses related to reduction in childhood infections. However, the findings of epidemiologic studies investigating the association between infection with atopy and asthma have been inconsistent. OBJECTIVE: We sought to investigate the effect of single or multiple infections (pathogen burden) on atopy and wheeze in urban children from Latin America. METHODS: Specific IgE against aeroallergens (sIgE) and skin prick test (SPT) reactivity for the most common local allergens were measured in 1128 children aged 4 to 11 years. Data on wheezing and potential confounders were collected by questionnaire. Infections by 8 pathogens were assessed by using serology and stool examination. Associations of wheeze and atopic outcomes with single and multiple infections were analyzed by means of logistic regression. RESULTS: Negative results for Toxoplasma gondii were associated with a higher prevalence of sIgE (≥0.70 kU/L), whereas negative results for Ascaris lumbricoides, T gondii, herpes simplex virus, and EBV were associated with a higher prevalence of SPT reactivity. Children with 3 or fewer infection markers had a higher prevalence of sIgE and SPT reactivity compared with those with 4 or more infection markers. However, isolated infections or pathogen burden were not associated with the prevalence of atopic or nonatopic wheeze. CONCLUSION: The findings provide support for the idea that the hygiene hypothesis is operating in an urban Latin American context, but its expression is thus far restricted to the atopic status of patients and not the perceived asthma symptoms.

Correction: Prevalence and risk factors for asthma, rhinitis, eczema, and atopy among preschool children in an Andean city.

[This corrects the article DOI: 10.1371/journal.pone.0234633.].

Prevalence and risk factors for asthma, rhinitis, eczema, and atopy among preschool children in an Andean city.

BACKGROUND: Limited data are available on prevalence and associated risk factors for atopy and allergic diseases from high-altitude urban settings in Latin America. OBJECTIVE: To estimate the prevalence of atopy, asthma, rhinitis, and eczema, and associations with relevant risk factors in preschool children in the Andean city of Cuenca. METHODS: A cross-sectional study was undertaken using a representative sample of 535 children aged 3-5 years attending 30 nursery schools in the city of Cuenca, Ecuador. Data on allergic diseases and risk factors were collected by parental questionnaire. Atopy was measured by skin prick test (SPT) reactivity to a panel of relevant aeroallergens. Associations between risk factors and the prevalence of atopy and allergic diseases were estimated using multivariable logistic regression. RESULTS: Asthma symptoms were reported for 18% of children, rhinitis for 48%, and eczema for 28%, while SPT reactivity was present in 33%. Population fractions of asthma, rhinitis, and eczema attributable to SPT were 3.4%, 7.9%, and 2.9%, respectively. In multivariable models, an increased risk of asthma was observed among children with a maternal history of rhinitis (OR 1.85); rhinitis was significantly increased in children of high compared to low socioeconomic level (OR 2.09), among children with a maternal history of rhinitis (OR 2.29) or paternal history of eczema (OR 2.07), but reduced among children attending daycare (OR 0.64); eczema was associated with a paternal history of eczema (OR 3.73), and SPT was associated with having a dog inside the house (OR 1.67). CONCLUSIONS: A high prevalence of asthma, rhinitis, and eczema symptoms were observed among preschool children in a high-altitude Andean setting. Despite a high prevalence of atopy, only a small fraction of symptoms was associated with atopy. Parental history of allergic diseases was the most consistent risk factor for symptoms in preschool children.

Immunogenicity and protection induced by recombinant Toxocara canis proteins in a murine model of toxocariasis.

Toxocariasis, a natural helminth infection of dogs and cats caused by Toxocara canis and T. cati, respectively, that are transmitted to mammals, including humans. Infection control is based currently on periodic antihelmintic treatment and there is a need for the development of vaccines to prevent this infection. MATERIALS AND METHODS: Eight potential vaccine candidate T. canis recombinant proteins were identified by in silico (rTcGPRs, rTcCad, rTcVcan, rTcCyst) and larval proteomics (rTES26, rTES32, rMUC-3 and rCTL-4) analyses. Immunogenicity and protection against infectious challenge for seven of these antigens were determined in a murine model of toxocariasis. C57BL/6 female mice were immunized with each of or combinations of recombinant antigens prior to challenge with 500 T. canis embryonated eggs. Levels of specific antibodies (IgG, IgG1, IgG2a and IgE) in sera and cytokines (IL-5, INF-É£ and IL-10) produced by antigens-stimulated splenocytes, were measured. Presence of specific antibodies to the molecules was measured in sera of T. canis-seropositive dogs and humans. RESULTS: All seven molecules were immunogenic in immunized mice; all stimulated significantly elevated levels of specific IgG, IgG1 or IgG2a and six were associated with elevated levels of specific IgE; all induced elevated production of IFN- É£ and IL-10 by splenocytes, but only the in silico-identified membrane-associated recombinants (rTcCad, rTcVcan, and rTcCyst) induced significantly increased IL-5 production. Vaccination with two of the latter (rTcCad and rTcVcan) reduced larval loads in the T. canis challenged mice by 54.3% and 53.9% (P < 0.0001), respectively, compared to unimmunized controls. All seven recombinants were recognized by T. canis-seropositive dog and human sera. CONCLUSION: The identification of vaccine targets by in silico analysis was an effective strategy to identify immunogenic T. canis proteins capable of reducing larval burdens following challenge with the parasite. Two recombinant proteins, rTcCad and rTcVcan, were identified as promising vaccine candidates for canine toxocariasis.

Geohelminth infections: impact on allergic diseases.

Geohelminth infections are highly prevalent infections with a worldwide distribution. Epidemiological studies have shown an inverse relationship between geohelminth infection and allergy leading to the suggestion that geohelminths protect against allergy. A causal association is supported by the findings of intervention studies in humans and experimental animal models. Geohelminths cause chronic infections during which an intimate host-parasite interaction develops permitting the parasite to survive but protecting the host from damaging inflammation. Geohelminth parasites modulate allergic inflammation directed against parasite antigens and the same mechanisms may affect responses to inhalant aeroallergens. The mechanisms proposed to explain the allergy-modulatory effect of geohelminths include the induction of regulatory T cells and the creation of an immunosuppressive environment in relevant tissues. New treatments being considered for the treatment of asthma include live infections with hookworms. Insights provided by how geohelminths modulate inflammatory responses may allow the development of new treatments that mimic these effects.

Effects of helminth co-infections on atopy, asthma and cytokine production in children living in a poor urban area in Latin America.

BACKGROUND: Helminths are modulators of the host immune system, and infections with these parasites have been associated with protection against allergies and autoimmune diseases. The human host is often infected with multiple helminth parasites and most studies to date have investigated the effects of helminths in the context of infections with single parasite or types of parasites (e.g. geohelminths). In this study, we investigated how co-infections with three nematodes affect markers of allergic inflammation and asthma in children. We selected Ascaris lumbricoides and Trichuris trichiura, two parasites that inhabit the human intestine and Toxocara spp (Toxocara canis and/or T. cati), intestinal roundworms of dogs and cats that cause systemic larval infection in humans. These parasites were selected as the most prevalent helminth parasites in our study population. RESULTS: 36.4% of children were infected with one parasite; 12.7% with 2 and 5.2% with 3. Eosinophilia>4% and >10% was present in 74.3% and 25.5% of the children, respectively. Total IgE>200 IU/mL, sIgE≥0.70 kU/L and SPT positivity were present in 59.7%, 37.1% and 30% of the children, respectively. 22.7% had recent asthma (12.0% non-atopic and 10.7% atopic). Helminth infections were associated in a dose-dependent way to decrease in the prevalence of SPT and increase in eosinophilia, total IgE, and the production of the regulatory cytokine IL-10 by unstimulated peripheral blood leukocytes. No association with asthma was observed. CONCLUSIONS: Helminth co-infections in this population were associated with increased markers of the Th2 immune response, and with a host immune regulatory phenotype that may suppress allergic effector responses such as immediate hypersensitivity reactions in the skin.

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.