The Battle Between Influenza and the Innate Immune Response in the Human Respiratory Tract

Nicholls, John M

Endothelial cells in the past were considered as collateral damage when the process of DAD was initiated as a loss of the endothelial integrity with subsequent microvascular leakage was a key feature in bacterial sepsis and in viral infection such as H5N1 [67] . In the 2009 pandemic autopsy studies demonstrated viral antigen in endothelial cells and if the same can be demonstrated in H5N1 infection this may explain the extrapulmonary dissemination of virus in these infections [8] . It has also been shown that polarized endothelial cells can be infected in vitro [68] . Intriguingly recent publications have shown that endothelial cells may actually be involved in modulating the innate immune response via sphingosine-1phosphate signaling. This is a metabolite of sphingolipid and a ligand for G-protein coupled receptors SIP1-5 [69] . The role of these receptor ligands was shown by Marsolais and colleagues who used SIP ligands and found that they reduced the cytokine response using a mouse adapted influenza virus [70] . Further work demonstrated a level of SIP1 expression on lymphatic and vascular endothelial cells and that treatment with an agonist of SIP1 was able to reduce the production of chemokines CCL2, CCL5 and CD11b+ cells and decrease IFN γ secretion but did not affect IFNα, CCL2, IL6 or TNFα, thus showing that endothelial cells are able to actually modulate the inflammatory response [71] . It is possible that these SIP analogs may have a use in further therapies in dampening the excessive innate immune response [72] .