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Leet and Clara Guthrie Patterson Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000938","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Connecticut Children's Medical Center"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Immunol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Macrophages play prominent roles in bacteria recognition and clearance, including<jats:italic>Borrelia burgdorferi<\/jats:italic>(<jats:italic>Bb<\/jats:italic>), the Lyme disease spirochete. To elucidate mechanisms by which MyD88\/TLR signaling enhances clearance of<jats:italic>Bb<\/jats:italic>by macrophages, we studied wildtype (WT) and MyD88<jats:sup>\u2212\/\u2212<\/jats:sup><jats:italic>Bb<\/jats:italic>-stimulated bone marrow-derived macrophages (BMDMs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MyD88<jats:sup>\u2212\/\u2212<\/jats:sup>BMDMs exhibit impaired uptake of spirochetes but comparable maturation of phagosomes following internalization of spirochetes. RNA-sequencing of infected WT and MyD88<jats:sup>\u2212\/\u2212<\/jats:sup>BMDMs identified a large cohort of differentially expressed MyD88-dependent genes associated with re-organization of actin and cytoskeleton during phagocytosis along with several MyD88-independent chemokines involved in inflammatory cell recruitment. We computationally generated networks which identified several MyD88-dependent intermediate proteins (<jats:italic>Rhoq<\/jats:italic>and<jats:italic>Cyfip1<\/jats:italic>) that are known to mediate inflammation and phagocytosis respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings show that MyD88 signaling enhances, but is not required, for bacterial uptake or phagosomal maturation and provide mechanistic insights into how MyD88-mediated phagosomal signaling enhances<jats:italic>Bb<\/jats:italic>uptake and clearance.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12865-021-00418-8","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T11:02:56Z","timestamp":1621249376000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Macrophage mediated recognition and clearance of Borrelia burgdorferi elicits MyD88-dependent and -independent phagosomal signals that contribute to phagocytosis and inflammation"],"prefix":"10.1186","volume":"22","author":[{"given":"Sarah J.","family":"Benjamin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly L.","family":"Hawley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Vera-Licona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carson J.","family":"La Vake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge L.","family":"Cervantes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijun","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin D.","family":"Radolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3881-546X","authenticated-orcid":false,"given":"Juan C.","family":"Salazar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"issue":"13","key":"418_CR1","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1056\/NEJM198303313081302","volume":"308","author":"JL Benach","year":"1983","unstructured":"Benach JL, Bosler EM, Hanrahan JP, Coleman JL, Habicht GS, Bast TF, et al. 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