The hygiene hypothesis suggests that parasitic infection modulates host immune responses and decreases atopy, but other data suggest parasitic infections may induce allergic responsiveness as well. To investigate the impact of molecular similarity among allergens and cross-reactive homologous helminth proteins in IgE-based serologic assessment of allergic disorders in helminth-infected population, we used multiplexed assays in filarial-infected and non-infected individuals for IgE measurements to allergen extracts that contained proteins with high levels of homology with helminth proteins and IgE against representative recombinant allergens with and without helminth homologues were performed. The impact of helminth infection on the levels and function of the IgE to these specific homologous and non-homologous allergens was corroborated in an animal model. We found that having a tissue-invasive filarial infection increased the serological prevalence ofIgE directed against house dust mite and cockroach, but not against timothy grass, the latter with few allergens with homologues in helminth infection. IgE ELISA confirmed that filaria-infected individuals had higher IgE prevalences to those recombinant allergens that had homologues in helminths. Mice infected with helminth Heligmosomoides polygyrus displayed increased levels of IgE and positive skin tests to allergens with homologues in the parasite. These results show that cross-reactivity among allergens and helminth proteins can have practical implications altering serologic approaches to allergen testing and brings a new perspective to the Hygiene Hypothesis. We have extended these findings to the level of the T cell. Using cells from individuals with filarial infection (with or without allergic disease) and those from uninfected individuals (with or without allergic disease), we have shown that parasite antigen (and their aero-allergen orthologues) drives a CD4+ IL-4/IL-13 dominated response in filarial infection that is augmented when the subject is also allergic when measured using multiparameter flow cytometry or multiplexed cytokine measurements.

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19
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2015
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Bonne-Année, S; Nutman, T B (2018) Human innate lymphoid cells (ILCs) in filarial infections. Parasite Immunol 40:
Santiago, Helton da Costa; Nutman, Thomas B (2016) Role in Allergic Diseases of Immunological Cross-Reactivity between Allergens and Homologues of Parasite Proteins. Crit Rev Immunol 36:1-11
Santiago, Helton C; Nutman, Thomas B (2016) Human Helminths and Allergic Disease: The Hygiene Hypothesis and Beyond. Am J Trop Med Hyg 95:746-753
Gazzinelli-Guimarães, Pedro H; Bonne-Année, Sandra; Fujiwara, Ricardo T et al. (2016) Allergic Sensitization Underlies Hyperreactive Antigen-Specific CD4+ T Cell Responses in Coincident Filarial Infection. J Immunol 197:2772-9
Santiago, Helton da Costa; Ribeiro-Gomes, Flávia L; Bennuru, Sasisekhar et al. (2015) Helminth infection alters IgE responses to allergens structurally related to parasite proteins. J Immunol 194:93-100
O'Connell, Elise M; Nutman, Thomas B (2015) Eosinophilia in Infectious Diseases. Immunol Allergy Clin North Am 35:493-522
Herrick, Jesica A; Metenou, Simon; Makiya, Michelle A et al. (2015) Eosinophil-associated processes underlie differences in clinical presentation of loiasis between temporary residents and those indigenous to Loa-endemic areas. Clin Infect Dis 60:55-63
Makiya, Michelle A; Herrick, Jesica A; Khoury, Paneez et al. (2014) Development of a suspension array assay in multiplex for the simultaneous measurement of serum levels of four eosinophil granule proteins. J Immunol Methods 411:11-22
Mejia, Rojelio; Nutman, Thomas B (2012) Evaluation and differential diagnosis of marked, persistent eosinophilia. Semin Hematol 49:149-59
Santiago, Helton C; LeeVan, Elyse; Bennuru, Sasisekhar et al. (2012) Molecular mimicry between cockroach and helminth glutathione S-transferases promotes cross-reactivity and cross-sensitization. J Allergy Clin Immunol 130:248-56.e9

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