{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:11:33Z","timestamp":1785409893031,"version":"3.56.0"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2026,7,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Ehrlichia chaffeensis<\/jats:italic>\n                      is an obligately intracellular bacterium that repurposes multiple cellular signaling pathways, including Wnt, Hippo, Notch, and Hedgehog to evade innate immune defenses of mononuclear phagocytes. Although noncanonical Wnt signaling activation by\n                      <jats:italic toggle=\"yes\">E. chaffeensis<\/jats:italic>\n                      induces nuclear factor of activated T-cells (NFAT) activity, the functional consequences of this response have remained unclear. Here, we demonstrate that\n                      <jats:italic toggle=\"yes\">E. chaffeensis<\/jats:italic>\n                      exploits noncanonical Wnt\/Ca\n                      <jats:sup>2+<\/jats:sup>\n                      signaling to selectively activate NFATc1 and drive monocyte chemotactic chemokine production. In\n                      <jats:italic toggle=\"yes\">E. chaffeensis-<\/jats:italic>\n                      infected THP-1 cells, NFATc1 was exclusively activated, which was recapitulated in cells treated with soluble recombinant TRP120 (rTRP120) or TRP120 Wnt ligand short linear motif (SLiM) peptide (QDVASH). Correspondingly, significant increases and similar chemokine expression profiles were detected in THP-1 cells infected with\n                      <jats:italic toggle=\"yes\">E. chaffeensis<\/jats:italic>\n                      or treated with soluble rTRP120. Moreover, treatment with the NFATc1 peptide inhibitor (11R-VIVIT) significantly inhibited NFAT activation and chemokine expression. Consistent with a requirement for Wnt signaling, Frizzled 5 (FZD5)-deficient THP-1 cells exhibited reduced NFATc1 activation and diminished chemokine production and monocyte recruitment. Although the TRP120 Wnt ligand SLiM phenocopied\n                      <jats:italic toggle=\"yes\">E. chaffeensis-<\/jats:italic>\n                      induced NFATc1 activation, it was insufficient to independently stimulate chemokine production. In contrast, ectopic expression of TRP120-induced chemokine expression, which was further amplified by TRP120 Wnt SLiM treatment, indicating both TRP120-directed extracellular Wnt signaling and intracellular mechanisms are required. Collectively, these findings define a previously unrecognized pathogen-driven strategy that co-opts non-canonical Wnt\/NFAT signaling to promote monocyte chemotactic chemokine production.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Ehrlichia chaffeensis<\/jats:italic>\n                        is an obligately intracellular bacterium that causes human monocytic ehrlichiosis and survives within mononuclear phagocytes by manipulating key cell signaling pathways. Unlike most Gram-negative bacteria,\n                        <jats:italic toggle=\"yes\">E. chaffeensis<\/jats:italic>\n                        lacks classical pathogen-associated molecular patterns such as lipopolysaccharide and peptidoglycan, yet it stimulates strong chemokine production during infection; however, the molecular patterns, receptors and signaling pathways involved in inducing chemokine expression are unknown. Here, we uncover a cell signaling strategy whereby\n                        <jats:italic toggle=\"yes\">E. chaffeensis<\/jats:italic>\n                        , through TRP120 Wnt ligand mimicry, co-opts the noncanonical Wnt\/Ca\n                        <jats:sup>2+<\/jats:sup>\n                        signaling to selectively activate NFATc1 and drive chemokine expression. This pathogen-driven NFAT activation promotes monocyte recruitment, revealing a previously unrecognized chemokine induction mechanism.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msphere.00081-26","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T12:00:17Z","timestamp":1782129617000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["TRP120-dependent activation of noncanonical Wnt\/NFAT signaling drives monocyte chemokine production in\n                    <i>Ehrlichia chaffeensis<\/i>\n                    infection"],"prefix":"10.1128","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7817-0454","authenticated-orcid":true,"given":"Regina 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