The hygiene hypothesis suggests that parasitic infection modulates host immune responses and decreases atopy, but other data suggest parasitic infections may induce allergic responsiveness. To examine the molecular, structural, and immunologic relationships between parasite-encoded antigens and major aeroallergen homologues, parasite- and allergen-specific IgE, IgG, and IgG in sera of filaria-infected and filarial-uninfected atopic individuals were compared using multiple sets of parasite antigens and their aero-allergen homologues. For all sets of antigens there was a high degree of identity at the amino acid level, and overlapping predicted 3-dimensional structures .We found that filarial infection increased the serological prevalence IgE directed against house dust mite and cockroach, but not against timothy grass that appeared to be related to the presence of structural similarity between the allergens and the helminth proteins. IgE ELISA confirmed that 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. 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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18
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2014
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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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