Rapid activation of brainstem nuclei following TLR stimulation of the nasal mucosa.

We recently identified a novel neuroimmune mechanism in the nasal mucosa, in which activation of neuronal Toll‑like receptor (TLR) 7 results in upregulation of epithelial TLRs, via release of substance P. In the present study, we assessed whether intranasal challenge with the TLR7 agonist R‑837 additionally activated neurons in the central nervous system. Within one hour, R‑837 induced activation of the nucleus of the solitary tract, as well as a small increase in nasal IL‑6, but otherwise in the absence of an overt inflammatory response. It is tempting to speculate that it might be a direct interaction of R‑837 with trigeminal neurons in order to alert the central nervous system of invading pathogens.