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The binding of CCL2 to the surface of Trypanosoma cruzi induces chemo-attraction and morphogenesis
Authors:Yamauchi Lucy M  Aliberti Júlio C  Baruffi Marcelo D  Portela Ricardo W  Rossi Marcos A  Gazzinelli Ricardo T  Mineo José R  Silva João S
Affiliation:1. Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto-USP, Av. Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil;2. Division of Molecular Immunology, Cincinnati Children''s Hospital Medical Center and University of Cincinnati College of Medicine, 3333 Burnet Avenue, 45229-3039 Cincinnati, OH, USA;3. Department of Clinical Analysis, Toxicology and Bromatology, School of Pharmaceutical Sciences of Ribeirão Preto-USP, Av. Café s/n° 14040-903, Ribeirão Preto, SP, Brazil;4. Department of Biochemistry and Immunology, Institute of Biological Science, Universidade Federal of Minas Gerais, Av. Antonio Carlos, 6627, 31270-910 Belo Horizonte, MG, Brazil;5. Department of Pathology, School of Medicine of Ribeirão Preto-USP, Av. Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil;6. Laboratory of Immunology, Institute of Biomedical Science, Universidade Federal de Uberlândia, Av. Pará, 1.720, 38400-902 Uberlândia, MG, Brazil;1. Department of Pharmacy Practice, College of Pharmacy, WHO/PAHO Collaborating Centre for Traditional Medicine, University of Illinois at Chicago, USA;2. Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, India;3. Department of Cellular and Molecular Medicine, Rush University, Chicago, IL 60612, USA;4. Department of Pharmaceutical Microbiology, University of Ibadan, Ibadan, Nigeria;1. Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, 1425 San Pablo St, Los Angeles, CA 90089, USA;2. Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan;3. Department of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Abstract:Adhesion of Trypanosoma cruzi to host cells employs mechanisms which are complex and not completely understood. Upon infection, host cells release pro-inflammatory cytokines and chemokines in the environment. These had been found to be involved with increasing parasite uptake as well as killing by macrophages and cardiomyocytes. In the present study, we focused on the interaction of murine beta-chemokine CCL2 with trypomastigote forms of T. cruzi. We found that this chemokine directly triggers the chemotaxis and morphogenesis of trypomastigote forms of parasites. Binding assays showed that the interaction of CCL2 with molecules present in trypomastigote forms is abolished by the addition of condroitin 6-sulphate, a glycosaminoglycan. Moreover, we also observed that the parasite glycoproteins are the major players in this interaction. In summary, our study demonstrates a host ligand/parasite receptor interaction that may have relevant implications in the tissue tropism of this important parasitic disease.
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