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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.)

TLR9 agonist adsorbed to alum adjuvant prevents asthma-like responses induced by Blomia tropicalis mite extract

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Nunes, Fernanda P. B. [1] ; Alberca-Custodio, Ricardo Wesley [1] ; Gomes, Eliane [1] ; Fonseca, Denise M. [1] ; Yokoyama, Nicole H. [1] ; Labrada, Alexis [2] ; Russo, Momtchilo [1]
Total Authors: 7
[1] Univ Sao Paulo ICB USP, Inst Biomed Sci, Dept Immunol, Lab Immunobiol, Sao Paulo - Brazil
[2] Ctr Nacl Biopreparados, Dept Allergens, Havana - Cuba
Total Affiliations: 2
Document type: Journal article
Source: Journal of Leukocyte Biology; v. 106, n. 3, SI JULY 2019.
Web of Science Citations: 0

Blomia tropicalis mite is highly prevalent in tropical and subtropical regions and it is associated with allergic diseases such as rhinitis and asthma. By using an OVA-model of allergic lung disease, we have previously shown that sensitization in the presence of toll like receptors (TLRs) agonists attenuates subsequent OVA-induced allergic responses. Here, we evaluated the effect of CpG-ODN, a specific synthetic TLR-9 agonist, on the development of experimental asthma induced by Blomia tropicalis extract, a relevant source of aeroallergens. Among different protocols of Blomia tropicalis extract sensitization, the subcutaneous sensitization in the presence of alum adjuvant induced the highest Th2 responses, including high IgE levels. Adsorption of CpG to Blomia tropicalis extract/Alum attenuated the airway hyperreactivity, the infiltration of inflammatory cells including eosinophils, and the IL-5 content in BAL. In addition, lung peribronchial inflammatory infiltrate, mucus production and IL-5-producing CD3(+)CD4(+) T cells were significantly reduced in the Blomia tropicalis extract/Alum+CpG group. Importantly, CpG inhibited total IgE production as well as active systemic or cutaneous anaphylaxis reactions. Inhibition of pulmonary Th2 responses was associated with increased IL-10 production but not with IFN-gamma production. Notably, in IL-10-deficient mice, sensitization with OVA/Alum+CpG resulted in intense lung neutrophilia and IFN-gamma production, indicating that IL-10 is necessary to inhibit subsequent Th1 immunity. Our work highlights the mechanisms of allergy attenuation by CpG and it indicates the potential use of Alum-based formulation with CpG to treat allergic processes. (AU)

FAPESP's process: 15/16728-9 - Immunotherapy of experimental asthma by agonists of toll-like receptors
Grantee:Fernanda Peixoto Barbosa Nunes
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 15/25364-0 - Impact of infection-induced immunological scarring on the long-term host metabolic homeostasis
Grantee:Denise Morais da Fonseca
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 13/24694-1 - Immunotherapy of experimental asthma by agonists of toll-like receptors, infection or tolerance
Grantee:Momtchilo Russo
Support type: Research Projects - Thematic Grants
FAPESP's process: 16/16602-8 - Immunotherapy in experimental asthma by CpG
Grantee:Ricardo Wesley Alberca Custódio
Support type: Scholarships in Brazil - Doctorate