The interaction between helminth infection and allergic disease has been studied extensively using epidemiological tools coupled with physiological measurements of allergic disease and immunological assessments. We have demonstrated that chronic helminth infection protects against allergic diseases. Studies done to date have demonstrated the CD4+ cells (and neither the monocytes nor the basophils) are the overwhelmingly major source of IL-10 in chronic filarial infection. We have developed quantitative methods for examination of germline transcription for each of the antibody isotypes and have begun to use these methods to examine the molecular events that occur when antigens induce specific switch recombination events. Also baseline IgE and IgG4 germline transcription profiles have been measured in patients with allergic and parasitic infections and associated elevations of IgE and IgG4. An exhaustive search for parasite allergens that may cross-react with aeroallergens has been performed. We have identified a number of parasite antigens and the allergens orthologues and have studied the IgE and IgG responses to these. We have demonstrated unequivocally that parasite infections induced both parasite-specific IgE and IgE that interacts with environmental allergens to which the parasite antigens are closely related.

Project Start
Project End
Budget Start
Budget End
Support Year
15
Fiscal Year
2011
Total Cost
$362,953
Indirect Cost
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State
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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
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
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
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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