Sytemic and respiratory responses to intravenous or inhaled administration of flagellin in non-human primates
Respiratory delivery of the Toll-like receptor 5 agonist FLAMOD, a recombinant flagellin, offers a promising approach for treating bacterial pneumonia in mouse models. This study represents the first comprehensive assessment of FLAMOD delivered by nebulization in the non-human primate Macaca fascicularis. RNA sequencing was used to establish the transcriptional response across the respiratory tract (from the nose, trachea, bronchi to the lungs) and in the blood. The findings demonstrated that innate immunity, cytokine and chemokine signaling, and chemotaxis are key biological pathways modulated by FLAMOD in the respiratory tract. Blood transcriptional response overtime after nebulization was also analyzed and compared to the response observed after intravenous injection of FLAMOD.