title: Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells.
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.
authors: Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, 9700 RB, Groningen, The Netherlands.
authors: Mariana
authors: M
authors: Ruiz Silva
authors: Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, 9700 RB, Groningen, The Netherlands.
authors: Heidi
authors: H
authors: van der Ende-Metselaar
authors: Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, 9700 RB, Groningen, The Netherlands.
authors: H Lie
authors: HL
authors: Mulder
authors: Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, 9700 RB, Groningen, The Netherlands.
authors: Jolanda M
authors: JM
authors: Smit
authors: Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, 9700 RB, Groningen, The Netherlands.
authors: Izabela A
authors: IA
authors: Rodenhuis-Zybert
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D065632:Chikungunya Fever / Q000378:metabolism* / Q000473:pathology; D002646:Chikungunya virus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D005260:Female; D006801:Humans; D008297:Male; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D015854:Up-Regulation; D014709:Vero Cells
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2