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Type 1 classical DCs (cDC1), which depend on the transcription factor Batf3, are considered the main cross-presenting cells. In this study, we report that soluble Ags are efficiently cross-presented also by transcription factor SpiC-dependent red pulp macrophages (RPM) of the spleen. In contrast to cDC1, RPM used the mannose receptor for Ag uptake and employed the proteasome- and TAP-dependent cytosolic cross-presentation pathway, previously shown to be used in vitro by bone marrow\u2013derived DCs. In an in vivo vaccination model, both cDC1 and RPM cross-primed CTL efficiently but with distinct kinetics. Within a few days, RPM induced very early effector CTL of a distinct phenotype (Ly6A\/E+ Ly6C(+) KLRG1\u2212 CD127\u2212 CX3CR1\u2212 Grz-B+). In an adenoviral infection model, such CTL contained the early viral spread, whereas cDC1 induced short-lived effector CTL that eventually cleared the virus. RPM-induced early effector CTL also contributed to the endogenous antiviral response but not to CTL memory generation. In conclusion, RPM can contribute to antiviral immunity by generating a rapid CTL defense force that contains the virus until cDC1-induced CTL are available to eliminate it. This function can be harnessed for improving vaccination strategies aimed at inducing CTL.<\/jats:p>","DOI":"10.4049\/jimmunol.1900021","type":"journal-article","created":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T14:05:21Z","timestamp":1574863521000},"page":"87-100","source":"Crossref","is-referenced-by-count":34,"title":["Splenic Red Pulp Macrophages Cross-Prime Early Effector CTL That Provide Rapid Defense against Viral Infections"],"prefix":"10.1093","volume":"204","author":[{"given":"Marika","family":"Enders","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Experimentelle Immunologie, Rheinische Friedrich-Wilhelms-Universit\u00e4t , 53127 Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Franken","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Experimentelle Immunologie, Rheinische Friedrich-Wilhelms-Universit\u00e4t , 53127 Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Sophie","family":"Philipp","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Experimentelle Immunologie, Rheinische Friedrich-Wilhelms-Universit\u00e4t , 53127 Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Kessler","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Experimentelle Immunologie, Rheinische Friedrich-Wilhelms-Universit\u00e4t , 53127 Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann-Kathrin","family":"Baumgart","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Experimentelle Immunologie, Rheinische Friedrich-Wilhelms-Universit\u00e4t , 53127 Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Eichler","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Experimentelle Immunologie, Rheinische Friedrich-Wilhelms-Universit\u00e4t , 53127 Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel J H","family":"Wiertz","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, University Medical Center Utrecht , 3584 CX Utrecht ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalio","family":"Garbi","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Experimentelle Immunologie, Rheinische Friedrich-Wilhelms-Universit\u00e4t , 53127 Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Kurts","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Experimentelle Immunologie, Rheinische Friedrich-Wilhelms-Universit\u00e4t , 53127 Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,1,1]]},"reference":[{"key":"2025030417510290200_r1","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/ni0406-363","article-title":"Cross-priming","volume":"7","author":"Bevan","year":"2006","journal-title":"Nat. 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