Abstract
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-α/β 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 IFNβ in the chemokine secretion. We propose that balance between these soluble factors is imperative for an appropriate host response to CHIKV infection.
Highlights
MCP-1 is encoded by the ccl[2] gene and is produced in several cell types, including macrophages and fibroblasts[20]
Intracellular staining of MCP-1 confirmed the increase in expression of MCP-1 following Chikungunya virus (CHIKV) infection (Fig. 1b)
In this study we examined the role and the mechanism of MCP-1 production in CHIKV infection of peripheral blood mononuclear cells (PBMCs)
Summary
MCP-1 is encoded by the ccl[2] gene and is produced in several cell types, including macrophages and fibroblasts[20]. MCP-1-mediated migration of monocytes from the blood stream across the vascular endothelium is essential for routine immunological surveillance of tissues, as well as in response to inflammation[26]. MCP-1 knockout mice have impaired monocyte recruitment following intraperitoneal thioglycolate administration, as well as in response to viral infection including influenza A virus, coronavirus and West Nile virus (WNV)[27,28,29,30]. MCP-1 receptor knockout mice show increased cellular infiltration and develop more severe disease than wild type mice following infection with influenza virus, WNV and CHIKV31–33. CHIKV infection in whole blood stimulates MCP-1 production[37], the source and the mechanism of MCP-1 upregulation upon the infection remain elusive. We deciphered the source and mechanism of MCP-1 upregulation during CHIKV infection in human peripheral blood mononuclear cells (PBMCs)
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