| Popis: |
Dengue and chikungunya viruses (DENV and CHIKV) are among the most prevalent mosquito-borne viral pathogens affecting humans. The viruses are transmitted by the same mosquito vectors and co-circulate in the (sub)tropical areas of the world. They cause a similar acute febrile illness which in some cases as a result of aberrant inflammation, progress to severe diseases hallmarked by bleeding and organ impairment in case of DENV or chronic arthritis in case of CHIKV. Unfortunately, there is no specific treatment to prevent or mitigate disease progression. Moreover, the increasing number of DENV/CHIKV co infections have raised concerns of the how dual infections alter disease pathogenesis and presentation. Here, we elucidated the mechanisms underlying the innate immune response of human peripheral mononuclear blood cells to DENV and/or CHIKV infection. We demonstrated that simultaneous DENV/CHIKV co-infection suppressed CHIKV replication and led to an altered inflammatory response. In another study, we identified the mechanism leading to the production of MCP 1, a chemokine driving CHIKV-induced-arthritis. Finally, we show that CHIKV infection causes expansion of a specific blood monocyte subset that has been associated with several other chronic inflammatory diseases. Altogether, our work provided novel insights into inflammatory mechanisms triggered during mono and co infections with DENV and CHIKV and paved the way to define events that underlie the aberrant inflammation. Importantly, such knowledge will be instrumental in developing inflammation-balancing- strategies to treat these infections. |
