Chikungunya virus infection induces differential inflammatory and antiviral responses in human monocytes and monocyte-derived macrophages

Chikungunya virus (CHIKV) is a zoonotic arthropod-borne virus that has caused several outbreaks in tropical and subtropical areas worldwide during the last 50 years. The virus is known to target different human cell types throughout the course of infection including epithelial and endothelial cells, fibroblasts, primary monocytes and monocyte-derived macrophages (MDMs). The two latter are phagocytic cell populations of the innate immune system which are involved in some aspects of CHIKV pathogenesis. However, monocytes and macrophages also potentially contribute to the control of viral replication through the expression of different pattern recognition receptors sensing viral pathogens and subsequently, inducing an type I interferone (IFN-I)-dependent antiviral immune response. The aim of this study was to determine the modulation of the expression of Toll-like receptors (TLRs), cytokine secretion capabilities and antiviral factor production in monocytes and MDMs following infection with CHIKV. Moreover, we sought to determine the replication kinetics of CHIKV in these two cell populations. We found that the maximum peak of CHIKV replication was observed between 18- and 24-hours post-infection (hpi), while after that the is strongly reduced. Furthermore, CHIKV infection induced the pro-inflammatory cytokine production starting from the first 6 hpi in both monocytes and MDMs, with similar kinetics but different protein levels. In contrast, the kinetics of transcriptional expression of some TLRs were different between both cell types. In addition, IFN-I, 2',5'-oligoadenylate synthetase 1 (OAS1), and double-stranded RNA-activated protein kinase R (PKR) mRNA levels were detected in response to CHIKV infection of monocytes and MDMs, resulting the highest expression levels at 48 hpi. In conclusion, our data provides evidence that CHIKV infection activates the TLR pathways in primary monocytes and MDMs, which play a crucial role in CHIKV pathogenesis and/or host defense, differentially. However, additional studies are required to determine the functional role of TLRs in monocytes and MDMs.

Keywords: Antiviral activity; Chikungunya fever; Chikungunya virus; Double-stranded RNA; ISG; Inflammation; Toll-like receptors; interferon.