title: The absence of CCR7 results in dysregulated monocyte migration and immunosuppression facilitating chronic cutaneous leishmaniasis.
abstract: The protozoan parasite Leishmania major causes cutaneous lesions to develop at the site of infection, which are resolved with a strong Th1 immune response in resistant hosts, such as C57BL/6 mice. In contrast, the lesions ulcerate in susceptible hosts which display a Th2 response, such as BALB/c mice. The migration of cells in the immune response to L. major is regulated by chemokines and their receptors. The chemokine receptor CCR7 is expressed on activated DCs and naïve T cells, allowing them to migrate to the correct micro-anatomical positions within secondary lymphoid organs. While there have been many studies on the function of CCR7 during homeostasis or using model antigens, there are very few studies on the role of CCR7 during infection. In this study, we show that B6.CCR7(-/-) mice were unable to resolve the lesion and developed a chronic disease. The composition of the local infiltrate at the lesion was significantly skewed toward neutrophils while the proportion of CCR2(+) monocytes was reduced. Furthermore, a greater percentage of CCR2(+) monocytes expressed CCR7 in the footpad than in the lymph node or spleen of B6.WT mice. We also found an increased percentage of regulatory T cells in the draining lymph node of B6.CCR7(-/-) mice throughout infection. Additionally, the cytokine milieu of the lymph node showed a Th2 bias, rather than the resistant Th1 phenotype. This data shows that CCR7 is required for a protective immune response to intracellular L. major infection.
authors.affiliation: Menzies Research Institute, Hobart, Tasmania, Australia.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Kling
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
authors.forename: Heinrich
authors.initials: H
authors.lastname: Körner
mesh_terms: D000818:Animals; D002465:Cell Movement; D007111:Immunity, Cellular; D007165:Immunosuppression Therapy; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D009000:Monocytes / Q000276:immunology* / Q000502:physiology; D009504:Neutrophils / Q000276:immunology / Q000502:physiology; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7