NK cell activation in visceral leishmaniasis requires TLR9, myeloid DCs, and IL-12, but is independent of plasmacytoid DCs.

2.50
Hdl Handle:
http://hdl.handle.net/10033/17755
Title:
NK cell activation in visceral leishmaniasis requires TLR9, myeloid DCs, and IL-12, but is independent of plasmacytoid DCs.
Authors:
Schleicher, Ulrike; Liese, Jan; Knippertz, Ilka; Kurzmann, Claudia; Hesse, Andrea; Heit, Antje; Fischer, Jens A A; Weiss, Siegfried; Kalinke, Ulrich ( 0000-0003-0503-9564 ) ; Kunz, Stefanie; Bogdan, Christian
Abstract:
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)-alpha/beta 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-alpha/beta. Depletion of pDCs did not impair the activation of NK cells in L. infantum-infected mice. In contrast, L. infantum-induced NK cell cytotoxicity and IFN-gamma production were abolished in mDC-depleted mice. The same phenotype was observed in TLR9(-/-) mice, which lacked IL-12 expression by mDCs, and in IL-12(-/-) mice, whereas IFN-alpha/beta receptor(-/-) mice showed only a minor reduction of NK cell IFN-gamma expression. This study provides the first direct evidence that mDCs are essential for eliciting NK cell cytotoxicity and IFN-gamma release in vivo and demonstrates that TLR9, mDCs, and IL-12 are functionally linked to the activation of NK cells in visceral leishmaniasis.
Affiliation:
Institute of Medical Microbiology and Hygiene, University of Freiburg, D-79104 Freiburg, Germany.
Citation:
NK cell activation in visceral leishmaniasis requires TLR9, myeloid DCs, and IL-12, but is independent of plasmacytoid DCs. 2007, 204 (4):893-906 J. Exp. Med.
Journal:
The Journal of experimental medicine
Issue Date:
16-Apr-2007
URI:
http://hdl.handle.net/10033/17755
DOI:
10.1084/jem.20061293
PubMed ID:
17389237
Additional Links:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2118560
Type:
Article
Language:
en
ISSN:
0022-1007
Appears in Collections:
publications of the research group molecular Immunology (MOLI)

Full metadata record

DC FieldValue Language
dc.contributor.authorSchleicher, Ulrikeen
dc.contributor.authorLiese, Janen
dc.contributor.authorKnippertz, Ilkaen
dc.contributor.authorKurzmann, Claudiaen
dc.contributor.authorHesse, Andreaen
dc.contributor.authorHeit, Antjeen
dc.contributor.authorFischer, Jens A Aen
dc.contributor.authorWeiss, Siegfrieden
dc.contributor.authorKalinke, Ulrichen
dc.contributor.authorKunz, Stefanieen
dc.contributor.authorBogdan, Christianen
dc.date.accessioned2008-02-08T10:37:25Zen
dc.date.available2008-02-08T10:37:25Zen
dc.date.issued2007-04-16en
dc.identifier.citationNK cell activation in visceral leishmaniasis requires TLR9, myeloid DCs, and IL-12, but is independent of plasmacytoid DCs. 2007, 204 (4):893-906 J. Exp. Med.en
dc.identifier.issn0022-1007en
dc.identifier.pmid17389237en
dc.identifier.doi10.1084/jem.20061293en
dc.identifier.urihttp://hdl.handle.net/10033/17755en
dc.description.abstractNatural 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)-alpha/beta 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-alpha/beta. Depletion of pDCs did not impair the activation of NK cells in L. infantum-infected mice. In contrast, L. infantum-induced NK cell cytotoxicity and IFN-gamma production were abolished in mDC-depleted mice. The same phenotype was observed in TLR9(-/-) mice, which lacked IL-12 expression by mDCs, and in IL-12(-/-) mice, whereas IFN-alpha/beta receptor(-/-) mice showed only a minor reduction of NK cell IFN-gamma expression. This study provides the first direct evidence that mDCs are essential for eliciting NK cell cytotoxicity and IFN-gamma release in vivo and demonstrates that TLR9, mDCs, and IL-12 are functionally linked to the activation of NK cells in visceral leishmaniasis.en
dc.language.isoenen
dc.relation.urlhttp://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2118560en
dc.subject.meshAnimalsen
dc.subject.meshAntigens, CD11cen
dc.subject.meshCell Differentiationen
dc.subject.meshDNA, Protozoanen
dc.subject.meshDendritic Cellsen
dc.subject.meshFemaleen
dc.subject.meshInterferon-alphaen
dc.subject.meshInterferon-betaen
dc.subject.meshInterleukin-12en
dc.subject.meshKiller Cells, Naturalen
dc.subject.meshLeishmania donovanien
dc.subject.meshLeishmaniasis, Visceralen
dc.subject.meshLymphocyte Activationen
dc.subject.meshMiceen
dc.subject.meshMice, Knockouten
dc.subject.meshMyeloid Cellsen
dc.subject.meshPhenotypeen
dc.subject.meshReceptor, Interferon alpha-betaen
dc.subject.meshToll-Like Receptor 9en
dc.titleNK cell activation in visceral leishmaniasis requires TLR9, myeloid DCs, and IL-12, but is independent of plasmacytoid DCs.en
dc.typeArticleen
dc.contributor.departmentInstitute of Medical Microbiology and Hygiene, University of Freiburg, D-79104 Freiburg, Germany.en
dc.identifier.journalThe Journal of experimental medicineen

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