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Research Units - Infectious Diseases

Proteomics

Laboratory 2

Our laboratory studies macrophage function in the context of the mammalian host immune response to Borrelia burgdorferi. Our work is aimed at understanding the mechanisms of immune defense against infection, particularly focused on the activation of macrophages. We recently demonstrated that in C57Bl/6 mice, iNKT cell activation in response to B. burgdorferi is critical for the induction of IFN gamma in the cardiac tissue and protection against the development of acute carditis. IFNgamma activates macrophages locally inducing the production of proinflammatory factors and an increased phagocytic activity against the spirochete. We have also identified Complement Receptor (CR) 3 as a phagocytic receptor involved in the elimination of B. burgdorferi by macrophages. We have shown that CR3 cooperates with the GPI-anchored protein, CD14, in the internalization of the spirochete, a novel mechanism that we demonstrated is independent of MyD88 signals. We have also identified the co-chaperone MCJ as a major modulator of macrophage responses to B. burgdorferi. Our lab has also had a long interest in the role played by MAP kinases during inflammation. Two major projects of my lab consist on the characterization of the physiological role of the mitochondrial protein, MCJ, during pathological processes (infection, liver and heart pathologies) as well as its regulation, and the identification of the phagocitic 'ones' for B. burgdorferi, using different -omic techniques (differential proteomics, phosphoproteomics, microarrays...).

Ikerbasque Research Professor

Juan Anguita Castillo
  • Email: janguita@cicbiogune.es
  • Teléfono: 944.061.311 (EXT. 4211)
  • Address: Parque Tecnolgico de Vizcaya
    Ed. 801A Derio (Vizcaya)
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Laboratory members

Itziar Martín Ruíz

Technician

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Nicolas Navasa

Postdoctoral Researcher

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Julen Tomás Cortaza

PhD Student

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Estíbaliz Atondo

Technician

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Ana Carreras

PhD Student

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Miguel Angel Pascual

Technician

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Leticia Abecia Aliende

Postdoctoral Researcher

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Projects

Plan Nacional 2013-2015. Regulation of the macrophage response to infectious agents mediated by the cochaperone, MCJ

Macrophages are phagocytic cells that intervene critically as first-line defenders against infectious microorganisms. These cells are also responsible for certain pathologies, such as artherosclerosis. Increasing evidence points to a major role played by the metabolic status of these cells on their function. The cochaperone, MCJ (DNAJC15) is expressed by these cells and controls the activity of the respiratory chain, efectively modulating the ability of macrophages to respond to infectious agents. This project aims to understand the mechanisms of control of macrophage function as well as how the expression, and hence, the activity of this protein is regulated in these important cell type.

Gobierno Vasco 2013-2016. Induction of anergy by the tick salivary antigen, Salp15, and its therapeutic use in transplants.

The tick salivary protein, Salp15 is the best characterized antigen produced by this arthropod. Ticks are able to transmit several medically important diseases, which are endemic in parts of Europe, including Lyme borreliosis and anaplasmosis. Salp15 is an immunosuppressor that specifically acts on naive CD4 T cells, through its interaction with the domains D1D2 of CD4, which prevents the activation of these cells. We propose to address whether the interaction of Salp15 with CD4 T cells results in long-term unresponsiveness that could be beneficial for the treatment of pathologies in which these cells are a major player, such as rejection during transplantation.

ANTIDotE: Anti Tick Vaccines to Prevent Tick-Borne Diseases in Europe

Ticks transmit various types of bacteria, viruses and parasites with their bites and can cause diseases, among which tick-borne encephalitis (TBE), babesiosis and Lyme disease. There is still no vaccine for some of these diseases. In order to find a solution to this problem, a European initiative was started up recently, in which the Basque Center for Cooperative Research in Biosciences CIC bioGUNE is taking part. The project aims to identify compounds in ticks' saliva that may be used as active ingredients to develop a vaccine for multiple tick-borne diseases. Universities, companies and research centres from different European countries are taking part in this project, called ANTIDotE. It will last five years and has a budget of three million euros funded by the EU through the Seventh Framework Programme.

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Publications

N. Navasa, I. Martin, J.M. Iglesias-Pedraz, N. Beraza, E. Atondo, H. Izadi, F. Ayaz, S. Fernández-Alvarez, K. Hatle, A. Som, O. Dienz, B.A. Osborne, M.L. Martínez-Chantar, M. Rincon and J. Anguita; ; Regulation of oxidative stress by Methylation-controlled J protein controls macrophage responses to inflammatory insults . Journal of Infectious Diseases In Press (2014)


H. Sprong, J. Trentelman, I. Seemann, L. Grubhoffer, R.O.M. Rego, O. Hajduek, P. Kopácek, R. íma, A.M. Nijhof, J. Anguita, P. Winter, B. Rotter, S. Havlíková, B. Klempa, T.P. Schetters, J.W.R. Hovius; ANTIDotE: Anti-tick Vaccines to Prevent Tick-borne Diseases in Europe. Parasites and Vectors 7, 77 (2014)


Kung, F., J. Anguita, and U. Pal; Borrelia burgdorferi and tick proteins supporting pathogen persistence in the vector. Future Microbiology 8, 41 - 56 (2013)


K. Hatle, P. Gummadidala, N. Navasa, E. Bernardo, J. Dodge, B. Silverstrim, K. Fortner, E. Burg, B. Surat, J. Hammer, M. Radermacher, D.J. Taatjes, T. Thornton, J. Anguita, M. Rincon; MCJ/DnaJC15, an endogenous mitochondrial repressor of the respiratory chain that controls metabolic alterations. Molecular and Cellular Biology 33, 2302-2314 (2013)


K.L. Hawley, I. Martín-Ruiz, J.M. Iglesias-Pedraz, B. Berwin, J. Anguita; CD14 targets Complement Receptor 3 to lipid rafts during phagocytosis of Borrelia burgdorferi. International Journal of Biological Sciences 20, 803-810 (2013)