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Int J Biol Sci 2013; 9(8):803-810. doi:10.7150/ijbs.7136

Research Paper

CD14 Targets Complement Receptor 3 to Lipid Rafts during Phagocytosis of Borrelia burgdorferi

Kelly L. Hawley1, Itziar Martín-Ruiz2, Juan M. Iglesias-Pedraz1, Brent Berwin3, Juan Anguita1,2,4✉

1. Department of Veterinary and Animal Sciences, University of Massachusetts at Amherst, Amherst, MA 01003, USA.
2. Proteomics Unit, CIC bioGUNE. 48160 Derio, Bizkaia, Spain.
3. Department of Microbiology and Immunology. Dartmouth College of Medical Center. Lebanon, NH 03576, USA.
4. Ikerbasque, Basque Foundation for Science, 48003 Bilbao, Bizkaia, Spain.

Abstract

Phagocytosis of Borrelia burgdorferi, the causative agent of Lyme disease, is mediated partly by the interaction of the spirochete with Complement Receptor (CR) 3. CR3 requires the GPI-anchored protein, CD14, in order to efficiently internalize CR3-B. burgdorferi complexes. GPI-anchored proteins reside in cholesterol-rich membrane microdomains, and through its interaction with partner proteins, help initiate signaling cascades. Here, we investigated the role of CD14 on the internalization of B. burgdorferi mediated by CR3. We show that CR3 partly colocalizes with CD14 in lipid rafts. The use of the cholesterol-sequestering compound methyl-β-cyclodextran completely prevents the internalization of the spirochete in CHO cells that co-express CD14 and CR3, while no effect was observed in CD11b-deficient macrophages. These results show that lipid rafts are required for CR3-dependent, but not independent, phagocytosis of B. burgdorferi. Our results also suggest that CD14 interacts with the C-lectin domain of CR3, favoring the formation of multi-complexes that allow their internalization, and the use of β-glucan, a known ligand for the C-lectin domain of CR3, can compensate for the lack of CD14 in CHO cells that express CR3. These results provide evidence to understand the mechanisms that govern the interaction between CR3 and CD14 during the phagocytosis of B. burgdorferi.

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How to cite this article:
Hawley KL, Martín-Ruiz I, Iglesias-Pedraz JM, Berwin B, Anguita J. CD14 Targets Complement Receptor 3 to Lipid Rafts during Phagocytosis of Borrelia burgdorferi. Int J Biol Sci 2013; 9(8):803-810. doi:10.7150/ijbs.7136. Available from http://www.ijbs.com/v09p0803.htm