Journal Article

Lymphatic Vascularisation and Involvement of Lyve-1+ Macrophages in the Human Onchocerca Nodule

Attout, Tarik, Martinez, Valérie, Boussinesq, Michel, Bain, Odile, Mand, Sabine, Adjei, Ohene, Wanji, Samuel, Debrah, Alexander Yaw, Dénécé, Gaëlle, Hoerauf, Achim, Specht, Sabine, Martin, Coralie, Marfo-Debrekyei, Yeboah

2009

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Angiogenesis / Angiogenesis Inducing Agents - metabolism / Angiopoietin / Animals / Blindness / Blood / Blood vessels / Bone marrow / Cancer therapies / Cell Movement / Chemokines / Collaboration / CXCL12 protein / CXCR4 protein / Dermis - parasitology / Dermis - pathology / Endothelial cells / Endothelium / Endothelium, Lymphatic - metabolism / Endothelium, Lymphatic - parasitology / Female / Females / Gene expression / Humans / Immune response / Immunology / Immunology/Immunity to Infections / Infectious Diseases/Helminth Infections / Inflammation / Larvae / Leukocyte migration / Life Sciences / Ligands / Lymphatic system / Lymphatic Vessels - blood supply / Lymphatic Vessels - parasitology / Macrophages / Macrophages - metabolism / Macrophages - parasitology / Microbiology and Parasitology / Microfilariae - cytology / Neutrophils / Nodules / Onchocerca volvulus - cytology / Onchocerca volvulus - physiology / Onchocerciasis / Onchocerciasis - parasitology / Onchocerciasis - pathology / Ovarian cancer / Parasites / Parasitic diseases / Parasitology / Pathology/Immunology / Skin / Skin diseases / Tropical diseases / Tumors / Vascular endothelial growth factor / Vascularization / Vesicular Transport Proteins - metabolism / Wolbachia / Worms / Wound healing