Our results showed that the expression of TLR-4 was significantly upregulated on both CD14+CD16− and CD14+CD16+ monocyte subsets, and on CD14−CD16− subsets of macrophages in ZIKV immune animals at day 63 post-ZIKV infection (day 7 post-DENV-2) as compared to day 0 and 56 post-ZIKV infection (time points prior to DENV-2 infection) suggesting that DENV-2 infection was accompanied by a significant activation of inflammatory subsets of monocyte/macrophages. This evidence concerns the gene TLR4 and Zika virus infectious disease.