Intranasal administration of TLR agonists induces a discriminated local innate response along murine respiratory tract

Adjuvants are relevant for mucosal immunization in order to induce long lasting protective immunity. It has been shown that targeting to different regions of the airway results in different capacity to trigger adaptive/protective immunity. Nevertheless there is scarce knowledge regarding topological...

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Detalles Bibliográficos
Autores: Errea, Agustina Juliana, González Maciel, María Dolores, Hiriart, Yanina, Hozbor, Daniela Flavia, Rumbo, Martín
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/45801
Acceso en línea:http://hdl.handle.net/11336/45801
Access Level:acceso abierto
Palabra clave:Toll Like Receptors
Tlr Agonist
Airways
Innate Response
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
Descripción
Sumario:Adjuvants are relevant for mucosal immunization in order to induce long lasting protective immunity. It has been shown that targeting to different regions of the airway results in different capacity to trigger adaptive/protective immunity. Nevertheless there is scarce knowledge regarding topological responsiveness along airways to TLR agonists. We analyzed the effects of intranasal administration of lipopolysaccharide (LPS), poly I:C and flagellin on the expression of a panel of innate response markers along murine airways by laser microdissection and RTqPCR. In all cases treatment induced recruitment of inflammatory cells to airways. However, regional gene expression indicated that whereas deeper airways (mainly alveoli) respond with high expression of IL6, CXCL1 and CXCL10, the response in conductive airways (bronchi and bronchioles) is dominated by expression of CCL20. On the other hand, triggering TLR3 elicits a response dominated by CXCL10, showing higher expression at 6 h compared to 2 h, whereas LPS and flagellin induce a response peaking at 2 h and dominated by IL6 and CXCL1. The results presented here showed difference in topological response triggered by different TLR agonist. These results make the targeting of different sites of airways a variable to evaluate when selecting the appropriate combinations of TLR and vaccinal antigens for intranasal delivery.