title: CCR7 facilitates the pro-inflammatory function of dendritic cells in experimental leishmaniasis.
abstract: Cutaneous leishmaniasis, caused by the parasite Leishmania major, results in lesions at the site of infection, which are self-healing in resistant hosts. However, in the absence of the chemokine receptor CCR7, mice are unable to heal the lesion and develop chronic disease. These B6.CCR7(-/-) mice display an increased number of Th2 cells and immunosuppressive cytokine levels, as well as more regulatory T cells. As CCR7 is expressed on activated dendritic cells (DCs), and these cells require CCR7 to migrate to the draining lymph node, we expected decreased migration of DCs into the lymph node in the absence of CCR7 during cutaneous leishmaniasis. Consequently, in an attempt to initiate a self-healing response, we adoptively transferred CCR7(+) (B6.WT) DCs into the site of infection of B6.CCR7(-/-) mice. Surprisingly, instead of healing the lesion, B6.CCR7(-/-) mice inoculated with B6.WT DCs developed augmented lesions and showed increased immunosuppression compared to control B6.CCR7(-/-) mice transferred with B6.CCR7(-/-) DCs or B6.WT mice with B6.WT DCs. Finally, B6.WT mice injected with B6.CCR7(-/-) DCs also presented delayed healing of the lesion. These results indicate that CCR7 must be expressed on DCs, as well as peripheral cells, to allow an efficient immune response to L. major.
authors.affiliation: Menzies Research Institute Tasmania, Hobart, Tas, Australia; James Cook University, Townsville, Qld, Australia.
authors.forename: J C
authors.initials: JC
authors.lastname: Kling
authors.forename: J
authors.initials: J
authors.lastname: Darby
authors.forename: H
authors.initials: H
authors.lastname: Körner
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D054400:Receptors, CCR7 / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
chemical_list: C515371:Ccr7 protein, mouse; D016207:Cytokines; D054400:Receptors, CCR7
keywords: CCR7; Leishmania; dendritic cells