Altered monocyte response to the dengue virus in those with varying severity of past dengue infection

Objective: We sought to investigate the differences in monocyte immune responses to the dengue virus (DENV) in those who previously had either severe disease (past SD) or non-severe dengue (past NSD) following a secondary dengue infection. Method: Monocytes from healthy individuals who had either past SD (n=6) or past NSD (n=6) were infected at MOI one with all four DENV serotypes following incubation with autologous serum. 36-hours post infection, levels of inflammatory cytokines and viral loads were measured in the supernatant and expression of genes involved in viral sensing and interferon signaling was determined. Results: Monocytes of individuals with past SD produced significantly higher viral loads (p=0.0426 and cytokines (IL-10 p=0.008, IL-1 beta p=0.008 and IL-6 p=0.0411) when infected with DENV serotypes they were not immune to, compared to those who has past NSD. Monocytes of individuals with past SD also produced significantly higher viral loads (p=0.022) and cytokines (IL-10 p < 0.0001, IL-1 beta < 0.0001 and IL-6 p < 0.0001) when infected with DENV serotypes they were previously exposed to, despite the monocytes being infected in the presence of autologous serum. A significant upregulation of NLRP3 (p=0.005), RIG-I (0.0004) and IFNB-1 (0.01) genes were observed in those who had past SD compared to past NSD when infected with non-immune DENV serotypes. Conclusion: Monocytes from those with past SD appear to show marked differences in viral loads, viral sensing and production of inflammatory mediators in response to the DENV, when compared to those who experienced past NSD, suggesting that initial innate immune responses may influence the disease outcome.