Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cellsSilva, M. R., van der Ende-Metselaar, H., Mulder, H. L., Smit, J. M. & Rodenhuis-Zybert, I. A., 25-Aug-2016, In : Scientific Reports. 6, 9 p., 32288.
Research output: Contribution to journal › Article › Academic › peer-review
Monocyte chemoattractant protein-1 (MCP-1/CCL2)-mediated migration of monocytes is essential for immunological surveillance of tissues. During chikungunya virus (CHIKV) infection however, excessive production of MCP-1 has been linked to disease pathogenesis. High MCP-1 serum levels are detected during the viremic phase of CHIKV infection and correlate with the virus titre. In vitro CHIKV infection was also shown to stimulate MCP-1 production in whole blood; yet the role and the mechanism of MCP-1 production upon infection of human peripheral blood mononuclear cells remain unknown. Here we found that active CHIKV infection stimulated production of MCP-1 in monocytes. Importantly however, we found that communication with other leukocytes is crucial to yield MCP-1 by monocytes upon CHIKV infection. Indeed, blocking interferon-alpha/beta receptor or the JAK1/JAK2 signalling downstream of the receptor abolished CHIKV-mediated MCP-1 production. Additionally, we show that despite the apparent correlation between IFN type I, CHIKV replication and MCP-1, modulating the levels of the chemokine did not influence CHIKV infection. In summary, our data disclose the complexity of MCP-1 regulation upon CHIKV infection and point to a crucial role of IFN beta in the chemokine secretion. We propose that balance between these soluble factors is imperative for an appropriate host response to CHIKV infection.
|Number of pages||9|
|Publication status||Published - 25-Aug-2016|
- CHEMOATTRACTANT PROTEIN-1 MCP-1, MONOCYTE CHEMOTACTIC PROTEIN-1, CYTOKINE EXPRESSION, DIFFERENTIAL ROLES, CCR2 DEFICIENCY, MOUSE MODEL, BONE LOSS, DISEASE, CHEMOKINES, ARTHRITIS