Expression of interleukin-6 family receptors in NK92 cells is regulated by cytokines and not through direct interaction with Plasmodium falciparum-infected erythrocytes.

A balanced proinflammatory cytokine response to Plasmodium ssp. infection is crucial to control the disease outcome. To elucidate the effect of cytokines and Plasmodium falciparum-infected erythrocytes on the regulation of interleukin (IL)-6 receptor (IL-6R), ciliary neurotrophic factor alpha (CNTFR-α) and glycoprotein (gp)130 in natural killer (NK) cells in the context of malaria, we assessed their gene expression and surface expression in NK92 cells. P. falciparum alone did not alter gene expression of the investigated receptors in NK92 cells. Analysis revealed a low effect of IL-6 on IL-6R surface expression in NK92 cells. However, at transcriptional level, a downregulation of IL-6R was observed following IL-6 stimulation. Thus, IL-6 might act within a negative feedback loop to terminate signal transduction by downregulating IL-6R expression. Additionally, we observed that IL-6R and CNTFR-α surface expression were regulated by a combination of IL-2, 12, and 18, and gp130 was influenced by interferon-α. Our results show that the IL-6 family receptors in NK92 cells are not directly influenced by P. falciparum. However, cytokines usually derived from accessory cells during malaria episodes may regulate IL-6 receptor signaling pathways. This finding encourages future studies in a more physiological context and with primary cells isolated from humans with and without malaria.

Citation

Evelyn Böttger, Elisandra Grangeiro de Carvalho, Stefanie Meese, Jürgen F J Kun, Meral Esen. Expression of interleukin-6 family receptors in NK92 cells is regulated by cytokines and not through direct interaction with Plasmodium falciparum-infected erythrocytes. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research. 2013 Feb;33(2):65-71

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PMID: 23398366

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