| Texto completo | |
| Autor(es): |
Mirotti, Luciana Cristina
;
Alberca Custdio, Ricardo Wesley
;
Gomes, Eliane
;
Rammauro, Florencia
;
de Araujo, Eliseu Frank
;
Garcia Calich, Vera Lucia
;
Russo, Momtchilo
Número total de Autores: 7
|
| Tipo de documento: | Artigo Científico |
| Fonte: | FRONTIERS IN IMMUNOLOGY; v. 8, FEB 3 2017. |
| Citações Web of Science: | 9 |
| Resumo | |
Aluminum-containing adjuvants usually referred as Alum are considered as T helper type-2 (Th2) adjuvants, while agonists of toll-like receptors (TLRs) are viewed as adjuvants that favor Th1/Th17 immunity. Alum has been used in numerous vaccine formulations; however, its undesired pro-Th2 adjuvant activity constitutes a caveat for Alum-based vaccines. Combining Alum with TLR-dependent, pro-Th1/Th17 adjuvants might dampen the pro-Th2 activity and improve the effectiveness of vaccine formulations. Here, using the ovalbumin (OVA) model of allergic lung inflammation, we found that sensitization with the synthetic TLR9 agonist, which is composed of oligodeoxynucleotides containing CpG motifs adsorbed to Alum, inhibited the development of OVA-induced lung allergic Th2 responses without shifting toward a Th1 pattern. The conversion of T cell immunity from the polarized allergic Th2 response to a non-polarized form by sensitization with OVA/ Alum/CpG was dependent on MyD88 signaling in myeloid cells. Notably, sensitization of IL-10-deficient mice with OVA/Alum/CpG resulted in the development of neutrophilic lung inflammation associated with IFN gamma production. However, in IL-10/IL-12-deficient mice, it resulted in neutrophilic inflammation dominated by IL-17 production. We conclude that OVA/Alum/CpG sensitization signaling via MyD88 and IL-10 molecules results in non-polarized immunity. Conversely, OVA/Alum/CpG sensitization in presence of MyD88 but absence of IL-10 or IL-10/IL-12 molecules results, respectively, in neutrophilic inflammation associated with IFN gamma or IL-17 production. Our work provides novel OVA models of lung inflammation and suggests that Alum/CpG-based formulations might be of potential use in anti-allergic or anti-infectious processes. (AU) | |
| Processo FAPESP: | 10/11071-8 - Modulação da reação alérgica pulmonar por ligantes endógenos de receptores do tipo toll 4 (tlr4) |
| Beneficiário: | Luciana Cristina Mirotti |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 16/16602-8 - Imunoterapia na asma experimental por CpG |
| Beneficiário: | Ricardo Wesley Alberca Custódio |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 13/24694-1 - Imunoterapia na asma experimental por agonistas de receptores toll-like, infecção ou tolerância |
| Beneficiário: | Momtchilo Russo |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |