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2020-11-13
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IFN-γ-MEDIATED EFFICACY OF ALLERGEN-FREE IMMUNOTHERAPY USING MYCOBACTERIAL ANTIGENS AND CPG-ODN
Fonseca, Denise M. et al. | Date Issued: 2011
Author
Fonseca, Denise M.
Paula, Marina O.
Wowk, Pryscilla F.
Campos, Lívia W.
Gembre, Ana F.
Turato, Walter M.
Ramos, Simone G.
Dias-Baruffi, Marcelo
Barboza, Renato
Gomes, Eliane
Horn, Cynthia
Marchal, Gilles
Arruda, Luisa K.
Russo, Momtchilo
Bonato, Vânia L. D.
Affilliation
University of São Paulo. School of Medicine of Ribeirão Preto. Department of Biochemistry and Immunology. Ribeirão Preto, SP, Brazil.
University of São Paulo. School of Medicine of Ribeirão Preto. Department of Biochemistry and Immunology. Ribeirão Preto, SP, Brazil.
University of São Paulo. School of Medicine of Ribeirão Preto. Department of Biochemistry and Immunology. Ribeirão Preto, SP, Brazil.
University of São Paulo. School of Medicine of Ribeirão Preto. Department of Biochemistry and Immunology. Ribeirão Preto, SP, Brazil.
University of São Paulo. School of Medicine of Ribeirão Preto. Department of Biochemistry and Immunology. Ribeirão Preto, SP, Brazil.
University of São Paulo. School of Medicine of Ribeirão Preto. Department of Biochemistry and Immunology. Ribeirão Preto, SP, Brazil.
University of São Paulo. School of Medicine of Ribeirão Preto. Department of Pathology. Ribeirão Preto, SP, Brazil.
University of São Paulo. School of Pharmaceutical Sciences of Ribeirão Preto. Department of Clinical, Toxicological, Bromatological Analyses. Ribeirão Preto, SP, Brazil.
University of São Paulo. Institute of Biomedical Sciences. Department of Immunology. São Paulo, SP, Brazil.
University of São Paulo. Institute of Biomedical Sciences. Department of Immunology. São Paulo, SP, Brazil.
Fundação Osvaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Institute Pasteur. Immunotherapix Bio Top. Paris, France.
University of São Paulo. School of Medicine of Ribeirão Preto. Department of Medicine. Division of Clinical Immunology. Ribeirão Preto, SP, Brazil.
University of São Paulo. Institute of Biomedical Sciences. Department of Immunology. São Paulo, SP, Brazil.
University of São Paulo. School of Medicine of Ribeirão Preto. Department of Biochemistry and Immunology. Ribeirão Preto, SP, Brazil.
Abstract
Epidemiological and experimental evidence supports the notion that microbial infections that are known to induce Th1-type immune responses can suppress Th2 immune responses, which are characteristics of allergic disorders. However, live microbialimmunization might not be feasible for human immunotherapy. Here, we evaluated whether induction of Th1 immunity by the immunostimulatory sequences of CpG-oligodeoxynucleotides (CpG-ODN), with or without culture filtrate proteins (CFP), from Mycobacterium tuberculosis would suppress ongoing allergic lung disease. Presensitized and ovalbumin (OVA)-challenged mice were treated subcutaneously with CpG, or CpG in combination with CFP (CpG/CFP). After 15 days of treatment, airway inflammation and specific T- and B-cell responses were determined. Cell transfer experiments were also performed. CpG treatment attenuated airway allergic disease; however, the combination CpG/CFP treatment was significantly more effective indecreasing airway hyperresponsiveness, eosinophilia and Th2 response. When an additional intranasal dose of CFP was given,allergy was even more attenuated. The CpG/CFP therapy also reduced allergen-specific IgG1 and IgE antibodies and increased IgG2a. Transfer of spleen cells from mice immunized with CpG/CFP also reduced allergic lung inflammation. CpG/CFP treatmentinduced CFP-specific production of IFN-cand IL-10 by spleen cells and increased production of IFN-γ in response to OVA. The essential role of IFN-cfor the therapeutic effect of CpG/CFP was evidenced in IFN-γ knockout mice. These results show thatCpG/CFP treatment reverses established Th2 allergic responses by an IFN-γ-dependent mechanism that seems to act bothlocally in the lung and systemically to decrease allergen-specific Th2 responses.
Keywords
Experimental Asthma
M. tuberculosis
Culture filtrate proteins
CpG-oligodeoxynucleotides
Allergen free immunotherapy
IFN-gamma
 
Publisher
Wiley
Citation
FONSECA, Denise M. et al. IFN-c-mediated efficacy of allergen-free immunotherapy using mycobacterial antigens and CpG-ODN. Immunology and Cell Biology, v. 89, p. 777-785, 2011.
DOI
10.1038/icb.2011.9
ISSN
0818-9641