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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

IFN-gamma-mediated efficacy of allergen-free immunotherapy using mycobacterial antigens and CpG-ODN

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Author(s):
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Fonseca, Denise M. [1] ; Paula, Marina O. [1] ; Wowk, Pryscilla F. [1] ; Campos, Livia W. [1] ; Gembre, Ana F. [1] ; Turato, Walter M. [1] ; Ramos, Simone G. [2] ; Dias-Baruffi, Marcelo [3] ; Barboza, Renato [4] ; Gomes, Eliane [4] ; Horn, Cynthia [5] ; Marchal, Gilles [6] ; Arruda, Luisa K. [7] ; Russo, Momtchilo [4] ; Bonato, Vania L. D. [1]
Total Authors: 15
Affiliation:
[1] Univ Sao Paulo, Dept Biochem & Immunol, Sch Med Riberao Preto, Ribeirao Preto - Brazil
[2] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pathol, Ribeirao Preto - Brazil
[3] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Toxicol Bromatol Anal, Ribeirao Preto - Brazil
[4] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Ribeirao Preto - Brazil
[5] Osvaldo Cruz Fdn, Evandro Chagas Res Inst, Rio De Janeiro - Brazil
[6] Inst Pasteur, Paris - France
[7] Univ Sao Paulo, Dept Med, Div Clin Immunol, Sch Med Ribeirao Preto, Ribeirao Preto - Brazil
Total Affiliations: 7
Document type: Journal article
Source: Immunology and Cell Biology; v. 89, n. 7, p. 777-785, OCT 2011.
Web of Science Citations: 10
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 microbial immunization 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 in decreasing 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 treatment induced CFP-specific production of IFN-gamma and IL-10 by spleen cells and increased production of IFN-gamma in response to OVA. The essential role of IFN-gamma for the therapeutic effect of CpG/CFP was evidenced in IFN-gamma knockout mice. These results show that CpG/CFP treatment reverses established Th2 allergic responses by an IFN-gamma-dependent mechanism that seems to act both locally in the lung and systemically to decrease allergen-specific Th2 responses. Immunology and Cell Biology (2011) 89, 777-785; doi:10.1038/icb.2011.9; published online 15 March 2011 (AU)