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

Abstract

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 6h compared to 2h, whereas LPS and flagellin induce a response peaking at 2h 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.

Keywords: Airways; Innate response; TLR agonist; Toll like receptors; Topological response.