title: Lymphatic vascularisation and involvement of Lyve-1+ macrophages in the human onchocerca nodule.
abstract: Onchocerciasis, caused by the filarial nematode Onchocerca volvulus, is a parasitic disease leading to debilitating skin disease and blindness, with major economic and social consequences. The pathology of onchocerciasis is principally considered to be a consequence of long-standing host inflammatory responses. In onchocerciasis a subcutaneous nodule is formed around the female worms, the core of which is a dense infiltrate of inflammatory cells in which microfilariae are released. It has been established that the formation of nodules is associated with angiogenesis. In this study, we show using specific markers of endothelium (CD31) and lymphatic endothelial cells (Lyve-1, Podoplanin) that not only angiogenesis but also lymphangiogenesis occurs within the nodule. 7% of the microfilariae could be found within the lymphatics, but none within blood vessels in these nodules, suggesting a possible route of migration for the larvae. The neovascularisation was associated with a particular pattern of angio/lymphangiogenic factors in nodules of onchocerciasis patients, characterized by the expression of CXCL12, CXCR4, VEGF-C, Angiopoietin-1 and Angiopoietin-2. Interestingly, a proportion of macrophages were found to be positive for Lyve-1 and some were integrated into the endothelium of the lymphatic vessels, revealing their plasticity in the nodular micro-environment. These results indicate that lymphatic as well as blood vascularization is induced around O. volvulus worms, either by the parasite itself, e.g. by the release of angiogenic and lymphangiogenic factors, or by consecutive host immune responses.
authors.affiliation: USM 307, Parasitologie comparée et Modèles expérimentaux, Muséum National d'Histoire Naturelle, Paris, France.
authors.forename: Tarik
authors.initials: T
authors.lastname: Attout
authors.forename: Achim
authors.initials: A
authors.lastname: Hoerauf
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Dénécé
authors.forename: Alexander Yaw
authors.initials: AY
authors.lastname: Debrah
authors.forename: Yeboah
authors.initials: Y
authors.lastname: Marfo-Debrekyei
authors.forename: Michel
authors.initials: M
authors.lastname: Boussinesq
authors.forename: Samuel
authors.initials: S
authors.lastname: Wanji
authors.forename: Valérie
authors.initials: V
authors.lastname: Martinez
authors.forename: Sabine
authors.initials: S
authors.lastname: Mand
authors.forename: Ohene
authors.initials: O
authors.lastname: Adjei
authors.forename: Odile
authors.initials: O
authors.lastname: Bain
authors.forename: Sabine
authors.initials: S
authors.lastname: Specht
authors.forename: Coralie
authors.initials: C
authors.lastname: Martin
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D020405:Dermis / Q000469:parasitology / Q000473:pathology; D004729:Endothelium, Lymphatic / Q000378:metabolism / Q000469:parasitology; D005260:Female; D006801:Humans; D042601:Lymphatic Vessels / Q000098:blood supply* / Q000469:parasitology; D008264:Macrophages / Q000378:metabolism* / Q000469:parasitology; D008842:Microfilariae / Q000166:cytology; D017181:Onchocerca volvulus / Q000166:cytology / Q000502:physiology; D009855:Onchocerciasis / Q000469:parasitology* / Q000473:pathology*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D043925:Angiogenesis Inducing Agents; C119248:LYVE1 protein, human; D033921:Vesicular Transport Proteins