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bioRxiv · 10.1101/2023.05.08.539843

A Yersinia effector activates JAK-STAT signaling in human macrophages

Berneking, L.·Bekere, I.·Schnapp, M.·Huang, J.·Ruckdeschel, K.·Aepfelbacher, M.
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Abstract

The multifunctional Yersinia effector YopM inhibits effector triggered immunity and increases production of the anti-inflammatory cytokine Interleukin-10 (IL-10) to suppress the host immune response. Previously it was shown that YopM induces IL-10 gene expression by elevating phosphorylation of the serine-threonine kinase RSK1 in the nucleus of human macrophages. Using transcriptomics, we now show that YopM affects expression of genes encoding components of the JAK-STAT signaling pathway. Further analysis revealed that YopM mediates nuclear translocation of the transcription factor Stat3 in Y. enterocolitica infected macrophages and that knockdown of Stat3 inhibited YopM-induced IL-10 gene expression. YopM-induced Stat3 translocation did not depend on autocrine IL-10, activation of RSK1 or tyrosine phosphorylation of Stat3. Thus, besides activation of RSK1, stimulation of nuclear translocation of Stat3 is another mechanism by which YopM increases IL-10 gene expression in macrophages.

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Berneking, L., Bekere, I., Schnapp, M., Huang, J., Ruckdeschel, K., Aepfelbacher, M.. 2023-05-09. A Yersinia effector activates JAK-STAT signaling in human macrophages. https://doi.org/10.1101/2023.05.08.539843

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