{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:29:22Z","timestamp":1791091762124,"version":"4.1.0"},"reference-count":78,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,4,16]]},"abstract":"<jats:p>Natural killer (NK) cells are sentinel components of the innate response to pathogens, but the cell types, pathogen recognition receptors, and cytokines required for their activation in vivo are poorly defined. Here, we investigated the role of plasmacytoid dendritic cells (pDCs), myeloid DCs (mDCs), Toll-like receptors (TLRs), and of NK cell stimulatory cytokines for the induction of an NK cell response to the protozoan parasite Leishmania infantum. In vitro, pDCs did not endocytose Leishmania promastigotes but nevertheless released interferon (IFN)-\u03b1\/\u03b2 and interleukin (IL)-12 in a TLR9-dependent manner. mDCs rapidly internalized Leishmania and, in the presence of TLR9, produced IL-12, but not IFN-\u03b1\/\u03b2. Depletion of pDCs did not impair the activation of NK cells in L. infantum\u2013infected mice. In contrast, L. infantum\u2013induced NK cell cytotoxicity and IFN-\u03b3 production were abolished in mDC-depleted mice. The same phenotype was observed in TLR9\u2212\/\u2212 mice, which lacked IL-12 expression by mDCs, and in IL-12\u2212\/\u2212 mice, whereas IFN-\u03b1\/\u03b2 receptor\u2212\/\u2212 mice showed only a minor reduction of NK cell IFN-\u03b3 expression. This study provides the first direct evidence that mDCs are essential for eliciting NK cell cytotoxicity and IFN-\u03b3 release in vivo and demonstrates that TLR9, mDCs, and IL-12 are functionally linked to the activation of NK cells in visceral leishmaniasis.<\/jats:p>","DOI":"10.1084\/jem.20061293","type":"journal-article","created":{"date-parts":[[2007,3,27]],"date-time":"2007-03-27T23:40:15Z","timestamp":1175038815000},"page":"893-906","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":152,"title":["NK cell activation in visceral leishmaniasis requires TLR9, myeloid DCs, and IL-12, but is independent of plasmacytoid DCs"],"prefix":"10.1084","volume":"204","author":[{"given":"Ulrike","family":"Schleicher","sequence":"first","affiliation":[{"name":"1Institute of Medical Microbiology and Hygiene, University of Freiburg, D-79104 Freiburg, Germany"},{"name":"2Institute of Clinical Microbiology, Immunology and Hygiene, University of Erlangen, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Liese","sequence":"additional","affiliation":[{"name":"1Institute of Medical Microbiology and Hygiene, University of Freiburg, D-79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilka","family":"Knippertz","sequence":"additional","affiliation":[{"name":"2Institute of Clinical Microbiology, Immunology and Hygiene, University of Erlangen, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Kurzmann","sequence":"additional","affiliation":[{"name":"1Institute of Medical Microbiology and Hygiene, University of Freiburg, D-79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Hesse","sequence":"additional","affiliation":[{"name":"1Institute of Medical Microbiology and Hygiene, University of Freiburg, D-79104 Freiburg, Germany"},{"name":"2Institute of Clinical Microbiology, Immunology and Hygiene, University of Erlangen, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje","family":"Heit","sequence":"additional","affiliation":[{"name":"3Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, 81675 Mu\u0308nchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens A.A.","family":"Fischer","sequence":"additional","affiliation":[{"name":"4Department of Research and Development, Miltenyi Biotec GmbH, 51429 Bergisch-Gladbach, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siegfried","family":"Weiss","sequence":"additional","affiliation":[{"name":"5Department of Molecular Immunology, Helmholtz Zentrum fu\u0308r Infektionsforschung, D-38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Kalinke","sequence":"additional","affiliation":[{"name":"6Department of Immunology, Paul Ehrlich Institute, 63225 Langen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Kunz","sequence":"additional","affiliation":[{"name":"1Institute of Medical Microbiology and Hygiene, University of Freiburg, D-79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Bogdan","sequence":"additional","affiliation":[{"name":"1Institute of Medical Microbiology and Hygiene, University of Freiburg, D-79104 Freiburg, Germany"},{"name":"2Institute of Clinical Microbiology, Immunology and Hygiene, University of Erlangen, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2007,3,26]]},"reference":[{"key":"2023072516021229400_BIB1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S095279150200002X","volume":"15","year":"2003","journal-title":"Curr. 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