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Phagocytosis of GFP-B. burgdorferi by murine Bone Marrow Macrophages (CM Olson)

 

 

 1. Proinflammatory signals in response to infection. Lyme disease is a highly prevalent infection in the United States. The disease is caused by the spirochete, Borrelia burgdorferi, which is transmitted by tick vectors, Ixodes scapularis and I. pacificus. Without proper treatment, the disease can evolve into inflammatory complications that most commonly affect the musculoskeletal, cardiovascular and nervous systems. Our lab is using the murine model of Lyme borreliosis to understand the role of signaling pathways such as NF-kB and MAP kinases in the development of proinflammatory responses in the context of infection. We are interested in the primary response to infectious agents triggered by their interaction with pattern recognition molecules, the effect of those interactions on the activation of iNKT and CD4 T cells, as well as the feedback mechanisms between both arms of the immune system. Part of our recent efforts are aimed at the understanding of the phagocytic uptake of the spirochete by macrophages (Figure).

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UMass Amherst

  

SAXS-derived structure of Salp15 (Ashish et al. JBC)

 2. Salp15 is a recently characterized antigen in tick saliva that has the capacity to inhibit the activation of naive CD4 T cells by repressing the calcium signals that arise upon TCR engagement. The final result is the inhibition of IL-2 production. Salp15 binds to the CD4 co-receptor on T cells and prevents early signals during activation. Our lab is currently analyzing the specificity of its function in murine as well as human T cells, and the potential application of this immunosuppressor in therapeutic intervention in several conditions that involve CD4 T cells.
   

Some of our manuscripts

 

  • A.T. Motameni, I.J. Juncadella, S.K. Ananthanarayanan, M.N. Hedrick, Y. Huet-Hudson, J. Anguita. 2004. Delivery of the immunosuppressive antigen, Salp15, to antigen presenting cells by Samonella typhimurium aroA mutants. Infection and Immunity. 72:3638-3642.

  • A.T. Motameni, T.C. Bates, I.J. Juncadella, C. Petty, M.N. Hedrick, J. Anguita. Distinct bacterial dissemination and disease outcome in mice subcutaneously infected with Borrelia burgdorferi in the midline of the back and the footpad. FEMS Immunology and Medical Microbiology. 45:279-284.

  • Ashish, R. Garg, J. Anguita, J.K. Krueger. 2006. Binding of full-length HIV-1 gp120 to CD4 induces structural reorientation around the gp120 core. Biophysical Journal. 91:L69-L71.

  • M.N. Hedrick, C.M. Olson, D. Conze, T.C. Bates, M. Rincon, J. Anguita. 2006. Control of Borrelia burgdorferi-specific CD4+ T cell effector function by IL-12- and TCR-induced p38 MAP kinase activity. Infection and Immunity. 74:5713-5717.

  • R. Garg, I.J. Juncadella, N. Ramamoorthi, Ashish, S.K. Ananthanarayanan, V. Thomas, M. Rincón, J.K. Krueger, E. Fikrig, C.M. Yengo, J. Anguita. 2006. Cutting Edge: CD4 is the receptor for the tick saliva immunosuppressor, Salp15. The Journal of Immunology. 177:6579-6583.

  • C.M. Olson, M.N. Hedrick, H. Izadi, T.C. Bates, E.R. Olivera, J. Anguita. 2007. p38 MAP kinase controls NF-kB transcriptional activation and TNFa production through RelA phosphorylation mediated by MSK1 in response to Borrelia burgdorferi antigens. Infection and Immunity. 75:270-277.

  • I.J. Juncadella, R. Garg, S.K. Ananthanarayanan, C.M. Yengo, J. Anguita. 2007. T cell signaling pathways inhibited by the tick saliva immunosuppressor, Salp15. FEMS Immunology and Medical Microbiology. 49:433-438.

  • H. Izadi, A.T. Motameni, T.C. Bates, E.R. Olivera, V. Villar-Suarez, I. Joshi, R. Garg, B.A. Osborne, R.J. Davis, M. Rincón, J. Anguita. 2007. c-Jun N-Terminal kinase 1 is required for toll-like receptor 1 gene expression in macrophages. Infection and Immunity. 75:5027-5034.

  • I.J. Juncadella, R. Garg, E.R. Olivera, J. Anguita. 2008. The Ixodes scapularis salivary protein, Salp15, prevents the association of HIV-1 gp120 and CD4. Biochemical and Biophysical Research Communications. 367:41-46.

  • Ashish, I.J. Juncadella, R. Garg, C.D. Boone, J. Anguita*, J.K. Krueger* (*Corresponding authors). 2008. Conformational rearrangement within the soluble domains of the CD4 receptor is ligand specific. The Journal of Biological Chemistry. 283:2761-2772.

  • C.M. Olson, T.C. Bates, H. Izadi, J.D. Radolf, S.A. Huber, J. Boyson, J. Anguita. 2009. Local production of Interferon gamma by invariant natural killer T cells modulates acute Lyme carditis. The Journal of Immunology. 182:3728-3734. doi:10.4049/jimmunol.0804111.
 

 

 

 

 

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