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

ERREA A; GONZALEZ MACIEL DOLORES; HIRIART YANINA; HOZBOR D; RUMBO M

IMMUNOLOGY LETTERS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2015

0165-2478

tAdjuvants are relevant for mucosal immunization in order to induce long lasting protective immu-nity. It has been shown that targeting to different regions of the airway results in different capacityto trigger adaptive/protective immunity. Nevertheless there is scarce knowledge regarding topologicalresponsiveness along airways to TLR agonists. We analyzed the effects of intranasal administration oflipopolysaccharide (LPS), poly I:C and flagellin on the expression of a panel of innate response markersalong murine airways by laser microdissection and RTqPCR. In all cases treatment induced recruitment ofinflammatory 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 air-ways (bronchi and bronchioles) is dominated by expression of CCL20. On the other hand, triggering TLR3elicits a response dominated by CXCL10, showing higher expression at 6 h compared to 2 h, whereas LPSand flagellin induce a response peaking at 2 h and dominated by IL6 and CXCL1. The results presentedhere showed difference in topological response triggered by different TLR agonist. These results make thetargeting of different sites of airways a variable to evaluate when selecting the appropriate combinationsof TLR and vaccinal antigens for intranasal delivery