{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:37:51Z","timestamp":1785411471496,"version":"3.56.0"},"posted":{"date-parts":[[2023,3,15]]},"group-title":"Microbiology","reference-count":53,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["1R21AI149723"],"award-info":[{"award-number":["1R21AI149723"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32GM153375"],"award-info":[{"award-number":["T32GM153375"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>Coxiella burnetii<\/jats:italic>\n                  is a highly infectious, aerosol-transmitted obligate intracellular bacterium that causes human Q fever and replicates within alveolar macrophages during pulmonary infection. Successful infection requires the\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  Type IVB secretion system (T4BSS), which delivers bacterial effector proteins into the host cytoplasm to remodel host processes and suppress the innate immune response. In the lung, IL-17 promotes antibacterial immunity by activating ACT1-TRAF6-dependent pathways that drive inflammatory gene expression, reactive oxygen species production, and neutrophil recruitment. However, how intracellular pathogens subvert IL-17 signaling pathways to promote survival within macrophages remains poorly understood. Here, we show that\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  evades IL-17-mediated host defense by targeting TRAF6, a central ubiquitin-dependent regulator of innate immune signaling. IL-17 signaling through ACT1-TRAF6 restricts\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  viability in macrophages; however,\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  impairs IL-17-induced NF-\u03baB and MAPK activation, particularly JNK phosphorylation.\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  T4BSS activity suppresses IL-17-driven reactive oxygen species production and neutrophil recruitment. We identify the\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  T4BSS effector EmcB as a TRAF6-targeting deubiquitinase that disrupts IL-17-dependent antimicrobial and chemotactic responses. Together these findings reveal that\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  downregulates intracellular innate immune signaling by targeting TRAF6, enabling evasion of the macrophage antimicrobial response and limiting neutrophil-mediated immunity.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance Statement<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Coxiella burnetii<\/jats:italic>\n                    causes Q fever and survives inside macrophages, immune cells that normally help eliminate inhaled pathogens. This study identifies a mechanism by which\n                    <jats:italic>C. burnetii<\/jats:italic>\n                    weakens macrophage defenses. We show that the bacterium disrupts macrophage IL-17 signaling, an immune pathway that promotes inflammatory gene expression, reactive oxygen species production, and neutrophil recruitment. Mechanistically,\n                    <jats:italic>C. burnetii<\/jats:italic>\n                    uses the secreted enzyme EmcB to target TRAF6, a central signaling protein required for IL-17-dependent antimicrobial responses. These findings reveal how an intracellular bacterial pathogen disables a key immune signaling hub to promote survival and limit innate immune activation, providing broader insight into how pathogens manipulate host immunity.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.03.15.532774","type":"posted-content","created":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T00:15:10Z","timestamp":1678925710000},"source":"Crossref","is-referenced-by-count":9,"title":["<i>Coxiella burnetii<\/i>\n                  deubiquitinates host TRAF6 to modulate the macrophage innate immune response"],"prefix":"10.64898","author":[{"given":"Arif","family":"Sadi","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, University of Nebraska Medical Center, Omaha, NE, US 68198"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana M.","family":"Clemente","sequence":"additional","affiliation":[{"name":"Department 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