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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,8,23]]},"abstract":"<jats:p>\n                    Sepsis, defined as organ dysfunction caused by a dysregulated host-response to infection, is characterized by immunosuppression. The vasopressor norepinephrine is widely used to treat low blood pressure in sepsis but exacerbates immunosuppression. An alternative vasopressor is angiotensin-II, a peptide hormone of the renin-angiotensin system (RAS), which displays complex immunomodulatory properties that remain unexplored in severe infection. In a murine cecal ligation and puncture (CLP) model of sepsis, we found alterations in the surface levels of RAS proteins on innate leukocytes in peritoneum and spleen. Angiotensin-II treatment induced biphasic, angiotensin-II type 1 receptor (AT1R)-dependent modulation of the systemic inflammatory response and decreased bacterial counts in both the blood and peritoneal compartments, which did not occur with norepinephrine treatment. The effect of angiotensin-II was preserved when treatment was delivered remote from the primary site of infection. At an independent laboratory, angiotensin-II treatment was compared in LysM-Cre AT1aR\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    (Myeloid-AT1a\n                    <jats:sup>\u2212<\/jats:sup>\n                    ) mice, which selectively do not express AT1R on myeloid-derived leukocytes, and littermate controls (Myeloid-AT1a\n                    <jats:sup>+<\/jats:sup>\n                    ). Angiotensin-II treatment significantly reduced post-CLP bacteremia in Myeloid-AT1a\n                    <jats:sup>+<\/jats:sup>\n                    mice but not in Myeloid-AT1a\n                    <jats:sup>\u2212<\/jats:sup>\n                    mice, indicating that the AT1R-dependent effect of angiotensin-II on bacterial clearance was mediated through myeloid-lineage cells. Ex vivo, angiotensin-II increased post-CLP monocyte phagocytosis and ROS production after lipopolysaccharide stimulation. These data identify a mechanism by which angiotensin-II enhances the myeloid innate immune response during severe systemic infection and highlight a potential role for angiotensin-II to augment immune responses in sepsis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2211370119","type":"journal-article","created":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T15:21:26Z","timestamp":1660576886000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":42,"title":["Angiotensin II enhances bacterial clearance via myeloid signaling in a murine sepsis model"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9670-9425","authenticated-orcid":false,"given":"Daniel E.","family":"Leisman","sequence":"first","affiliation":[{"name":"Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA 02114"},{"name":"Department of Medicine, Massachusetts General 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