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During infection with the intracellular bacterial pathogen\n                      <jats:italic toggle=\"yes\">Legionella pneumophila<\/jats:italic>\n                      , we previously found that GM-CSF enhances inflammatory cytokine production in murine monocytes and is required for\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      control of\n                      <jats:italic toggle=\"yes\">Legionella<\/jats:italic>\n                      . It is unclear whether GM-CSF similarly augments cytokine production in human monocytes during bacterial infection. Here, we find that GM-CSF enhances inflammatory cytokine expression in\n                      <jats:italic toggle=\"yes\">Legionella-<\/jats:italic>\n                      infected human monocytes by engaging multiple signaling pathways.\n                      <jats:italic toggle=\"yes\">Legionella<\/jats:italic>\n                      - and Toll-like receptor-dependent NF-\n                      <jats:inline-formula id=\"ui1\">\n                        <jats:alternatives>\n                          <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"iai.00565-24.im001.tif\"\/>\n                          <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" display=\"inline\" id=\"u1\" overflow=\"scroll\">\n                            <mml:mi>\u03ba<\/mml:mi>\n                          <\/mml:math>\n                        <\/jats:alternatives>\n                      <\/jats:inline-formula>\n                      B signaling is a prerequisite signal for GM-CSF to promote cytokine expression. Then, GM-CSF-driven Janus kinase 2\/signal transducer and activator of transcription 5 signaling is required to augment cytokine expression in\n                      <jats:italic toggle=\"yes\">Legionella<\/jats:italic>\n                      -infected human monocytes. We also found a role for phosphatidylinositol-3-kinase\/Akt\/mTORC1 signaling in GM-CSF-dependent upregulation of cytokine expression. Finally, glycolysis and amino acid metabolism are also critical for GM-CSF to boost cytokine gene expression. Our findings show that GM-CSF-mediated enhancement of cytokine expression in infected human monocytes is regulated by multiple signaling pathways, thereby allowing the host to fine-tune antibacterial immunity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00565-24","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T09:00:33Z","timestamp":1749114033000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["GM-CSF engages multiple signaling pathways to enhance pro-inflammatory cytokine responses in human monocytes during\n                    <i>Legionella<\/i>\n                    infection"],"prefix":"10.1128","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5134-3244","authenticated-orcid":false,"given":"V\u00edctor R.","family":"V\u00e1zquez Marrero","sequence":"first","affiliation":[{"name":"Department of Microbiology, 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