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Allergic Sensitization Underlies Hyperreactive Antigen-Specific CD4+ T Cell Responses in Coincident Filarial Infection.

ABSTRACT: Among the various hypotheses put forward to explain the modulatory influence of helminth infection on allergic effector responses in humans, the IL-10-induced suppression of Th2-associated responses has been the leading candidate. To explore this helminth/allergy interaction more fully, parasite- and allergen-specific CD4(+) T cell responses in 12 subjects with filarial infections, and coincident allergic sensitization (filarial [Fil](+)allergy [A](+)) were compared with the responses to three appropriate control groups (Fil(-)A(-) [n = 13], Fil(-)A(+) [n = 12], Fil(+)A(-) [n = 11]). The most important findings revealed that Fil(+)A(+) had marked (p < 0.0001 for all cytokines) increases in parasite Ag-driven Th2 (IL-4, IL-5, IL-13), Th9 (IL-9), and the regulatory (IL-10) cytokines when compared with Fil(+)A(-) Moreover, using multiparameter flow cytometry, filarial parasite Ag induced a marked increase in not only the frequency of CD4(+) T cells producing IL-4, IL-5, IL-2, and TNF-? in Fil(+)A(+) when compared with Fil(+)A(-) patients, but also in the frequencies of polyfunctional Th2-like (CD4(+)IL-4(+)IL-5(+) and CD4(+)IL-2(+)IL-4(+)IL-5(+)TNF-?(+)) cells. The Th2-associated responses seen in the Fil(+)A(+) group were correlated with serum IgE levels (p < 0.01, r = 0.5165 for IL-4; p < 0.001, r = 0.5544 for IL-5; and p < 0.001, r = 0.4901 for IL-13) and levels of circulating eosinophils (p < 0.0116, r = 0.5656) and their degranulation/activation products (major basic protein [p < 0.001, r = 0.7353] and eosinophil-derived neurotoxin [p < 0.01, r = 0.7059]). CD4(+) responses to allergen were not different (to a large extent) among the groups. Taken together, our data suggest that allergic sensitization coincident with filarial infection drives parasite Ag-specific T cell hyperresponsiveness, which is characterized largely by an augmented Th2-dominated immune response.

SUBMITTER: Gazzinelli-Guimaraes PH

PROVIDER: S-EPMC5026971 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Allergic Sensitization Underlies Hyperreactive Antigen-Specific CD4+ T Cell Responses in Coincident Filarial Infection.

Gazzinelli-Guimarães Pedro H PH Bonne-Année Sandra S Fujiwara Ricardo T RT Santiago Helton C HC Nutman Thomas B TB

Journal of immunology (Baltimore, Md. : 1950) 20160826 7

Among the various hypotheses put forward to explain the modulatory influence of helminth infection on allergic effector responses in humans, the IL-10-induced suppression of Th2-associated responses has been the leading candidate. To explore this helminth/allergy interaction more fully, parasite- and allergen-specific CD4(+) T cell responses in 12 subjects with filarial infections, and coincident allergic sensitization (filarial [Fil](+)allergy [A](+)) were compared with the responses to three a ...[more]

PMID: 27566825

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Project description:BackgroundInconsistent data exist regarding the influence of parasitic infection on the prevalence of allergic sensitization and disorders.ObjectiveTo investigate the impact of geohelminth and protozoan infections on sensitization patterns and allergic symptoms of children living in low-income communities in Gqeberha, South Africa.MethodsIn a cross-sectional study, 587 schoolchildren aged 8-12 years were recruited in June 2016 and screened for reactivity to common allergens by skin prick tests (SPTs) and for parasitic infections by stool examination. Additionally, questionnaires were completed to record allergic symptoms the children may have experienced.ResultsPositive SPTs were found in 237/587 children (40.4%), and about one-third of whom were polysensitized. Sensitizations were most frequently detected against the house dust mites (HDM) Dermatophagoides spp. (31.9%) and Blomia tropicalis (21.0%). Infections with geohelminths (Ascaris lumbricoides, Trichuris trichiura) were found in 26.8% and protozoan infections (Giardia intestinalis, Cryptosporidia spp.) in 13.9% of study participants. Mixed logistic regression analyses revealed negative associations between parasite infection and sensitization to Blomia tropicalis (OR: 0.54, 95% CI 0.33-0.89) and to Dermatophagoides spp. (OR 0.65, 95% CI 0.43-0.96), and between protozoan infection and allergic sensitization to any aeroallergen, although these associations were not significant when adjusted for false discovery. Geohelminth infection and intensity of geohelminth infection were both associated with reduced risk of polysensitization (OR 0.41, 95% CI 0.21-0.86), and this association remained significant with adjustment for false discovery. Reported respiratory symptoms were associated with HDM sensitization (ORs from 1.54 to 2.48), but not with parasite infection.Conclusions and clinical relevanceOur data suggest that geohelminth infection and high geohelminth infection intensity are associated with a reduced risk of polysensitization.

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Allergic Sensitization Underlies Hyperreactive Antigen-Specific CD4+ T Cell Responses in Coincident Filarial Infection.

Publications

Allergic Sensitization Underlies Hyperreactive Antigen-Specific CD4+ T Cell Responses in Coincident Filarial Infection.

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