"Investigating GM-CSF-dependent pro-inflammatory immune responses in human monocytes"

Victor R Vazquez Marrero and Sunny Shin

The proinflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) is required for host defense against a wide range of pathogens. Our laboratory has previously shown that in mice, monocytes are a key GM-CSF-responsive cell type. Mechanistically, GM-CSF engages JAK2/STAT5 signaling to enhance proinflammatory cytokine responses in murine monocytes during bacterial infection ex vivo. It is unclear whether a similar GM-CSF-mediated pathway also enhances the function of human monocytes. To investigate this, I treated primary human monocytes and a human monocytic cell line with GM-CSF followed by infection with the model bacterial pathogen Legionella pneumophila. I found that GM-CSF enhances the mRNA and protein levels of several key proinflammatory cytokines in human monocytes. Mechanistically, JAK2 is required for these responses. These findings show that GM-CSF-dependent JAK2 signaling can enhance proinflammatory cytokine production in human monocytes and highlight key similarities between murine and human monocytes immune responses, thus providing a basis for elucidating how GM-CSF enhances human-specific innate immune responses.