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Previous<jats:italic>in vivo<\/jats:italic>studies in murine cutaneous or visceral leishmaniasis showed that NK cells are activated by conventional dendritic cells in a Toll-like receptor 9-, interleukin-12 (IL-12)-, and IL-18-dependent manner during the early phase of infection and help to restrict the tissue parasite burden by unknown mechanisms. Here, we tested whether NK cells contribute to the control of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania<\/jats:named-content>infections by lysing or by activating infected host cells. Coculture experiments revealed that activated NK cells from poly(I:C)-treated mice readily killed tumor target cells, whereas<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania infantum<\/jats:named-content>- or<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">L. major<\/jats:named-content>-infected macrophages or dendritic cells remained viable. Infection with<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania<\/jats:named-content>did not significantly alter the expression of NK cell-activating molecules (retinoic acid early transcript alpha [Rae-1\u03b1], mouse UL16-binding protein-like transcript 1 [MULT-1], CD48) or inhibitory molecules (major histocompatibility complex [MHC] class I, nonclassical MHC class 1b molecule Qa-1) on the surface of myeloid cells, which offers an explanation for their protection from NK cell cytotoxicity. Consistent with these<jats:italic>in vitro<\/jats:italic>data,<jats:italic>in vivo<\/jats:italic>cytotoxicity assays revealed poor cytolytic activity of NK cells against adoptively transferred infected wild-type macrophages, whereas MHC class I-deficient macrophages were efficiently eliminated. NK cells activated by IL-12 and IL-18 stimulated macrophages to kill intracellular<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania<\/jats:named-content>in a cell contact-independent but gamma interferon-, tumor necrosis factor-, and inducible nitric oxide synthase-dependent manner. We conclude that<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania<\/jats:named-content>parasites, unlike viruses, do not render infected myeloid cells susceptible to the cytotoxicity of NK cells. Instead, soluble products of NK cells trigger the leishmanicidal activity of macrophages.<\/jats:p>","DOI":"10.1128\/iai.00079-11","type":"journal-article","created":{"date-parts":[[2011,4,26]],"date-time":"2011-04-26T02:39:56Z","timestamp":1303785596000},"page":"2699-2708","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":43,"title":["Leishmania-Infected Macrophages Are Targets of NK Cell-Derived Cytokines but Not of NK Cell Cytotoxicity"],"prefix":"10.1128","volume":"79","author":[{"given":"Chittappen K.","family":"Prajeeth","sequence":"first","affiliation":[{"name":"Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, and Universit\u00e4tsklinikum Erlangen, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Haeberlein","sequence":"additional","affiliation":[{"name":"Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, and Universit\u00e4tsklinikum Erlangen, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Sebald","sequence":"additional","affiliation":[{"name":"Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, and Universit\u00e4tsklinikum Erlangen, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Schleicher","sequence":"additional","affiliation":[{"name":"Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, and Universit\u00e4tsklinikum Erlangen, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Bogdan","sequence":"additional","affiliation":[{"name":"Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, and Universit\u00e4tsklinikum Erlangen, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2005.01681.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100921"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20051474"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001486"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1001-907"},{"key":"e_1_3_2_7_2","first-page":"367","volume-title":"Phagocyte-pathogen interaction","author":"Bogdan C","year":"2009","unstructured":"BogdanC. 2009. 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