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How these very diverse functions are regulated remains unknown. This study, using the lymphocytic choriomeningitis virus, showed that a subset of CD169<jats:sup>+<\/jats:sup> macrophages in murine spleen and lymph nodes produced high amounts of IFN-I upon infection. Absence of CD169<jats:sup>+<\/jats:sup> macrophages led to insufficient production of IFN-I, lower antiviral activity and persistence of virus. Lack of CD169<jats:sup>+<\/jats:sup> macrophages also limited the IFN-I-dependent expression of PD-L1. Enhanced viral replication in the absence of PD-L1 led to persistence of virus and prevented CD8<jats:sup>+<\/jats:sup> T-cell exhaustion. As a consequence, mice exhibited severe immunopathology and died quickly after infection. Therefore, CD169<jats:sup>+<\/jats:sup> macrophages are important contributors to the IFN-I response and thereby influence antiviral activity, CD8<jats:sup>+<\/jats:sup> T-cell exhaustion and immunopathology.<\/jats:p>","DOI":"10.1038\/cddis.2016.350","type":"journal-article","created":{"date-parts":[[2016,11,3]],"date-time":"2016-11-03T13:45:17Z","timestamp":1478180717000},"page":"e2446-e2446","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["CD169+ macrophages regulate PD-L1 expression via type I interferon and thereby prevent severe immunopathology after LCMV infection"],"prefix":"10.1038","volume":"7","author":[{"given":"Namir","family":"Shaabani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikas","family":"Duhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal","family":"Khairnar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmae","family":"Gassa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Ferrer-Tur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"H\u00e4ussinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Recher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennadiy","family":"Zelinskyy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Dittmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirko","family":"Trilling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Scheu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Hardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp A","family":"Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Honke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl S","family":"Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,11,3]]},"reference":[{"key":"BFcddis2016350_CR1","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/nri1573","volume":"5","author":"B Rehermann","year":"2005","unstructured":"Rehermann B, Nascimbeni M . 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