Protection of mouse by blockade to TNF-α signaling is due to inhibition against IL-17A

We have previously reported that the dengue virus (DENV) type 3 P12/08 strain caused a lethal systemic infection, severe vascular leakage at terminal stage in IFN-α/β and γ receptors knockout mice (IFN-α/β/γRKO mice), and blockade of TNF-α signaling drastically protected mice. However, the detailed pathological mechanism remains unknown. Therefore, we performed transcriptome analysis of liver and intestinal specimens, which showed most clearly exhibited vascular leakage, chronologically collected from infected- IFN-α/β/γRKO mice with/without anti-TNF-α Ab treatment. We applied mouse microarray to profile global gene expression of liver and small intestine of four mouse groups, DENV-3 P12/08 infected mouse Day 3 and 4 p.i. with or without anti-TNF-α Ab treatment, and mock-infected mice.