TLR9 signaling is essential for the innate NK cell response in murine cutaneous leishmaniasis.
Mice deficient for the TLR adaptor molecule MyD88 succumb to a local infection with Leishmania (L.) major. However, the TLR(s) that contribute to the control of this intracellular parasite remain to be defined. Here, we show that TLR9 was required for the induction of IL-12 in bone marrow-derived DC by intact L. major parasites or L. major DNA and for the early IFN-gamma expression and cytotoxicity of NK cells following infection with L. major in vivo. During the acute phase of infection TLR9-/- mice exhibited more severe skin lesions and higher parasite burdens than C57BL/6 wild-type controls. Although TLR9 deficiency led to a transient increase of IL-4, IL-13 and arginase 1 mRNA and a reduced expression of iNOS at the site of infection and in the draining lymph nodes, it did not prevent the development of Th1 cells and the ultimate resolution of the infection. We conclude that TLR9 signaling is essential for NK cell activation, but dispensable for a protective T cell response to L. major in vivo.
Liese
Jan
J
Institute of Medical Microbiology and Hygiene, Department of Medical Microbiology and Hygiene, University Clinic of Freiburg, Freiburg, Germany.
Schleicher
Ulrike
U
Bogdan
Christian
C
D000818:Animals; D001119:Arginase / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics; D018793:Interleukin-13 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D018314:Leishmania infantum / Q000276:immunology*; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D012867:Skin / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D018793:Interleukin-13; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D001119:Arginase