Email: janguita@vasci.umass.edu
D. Anguita Vet and Animal Science Dept Web Site

Ph.D.: University of Leon, Spain,
Postdoctoral Training: Yale University School of Medicine

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- k B 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 and differentiation of CD4 T cells, as well as the feedback mechanisms between both arms of the immune system.

Immunosuppression mediated by Salp15

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. Our lab is currently analyzing the early events that are affected by Salp15, the specificity of its function in murine as well as human T cells, as well as the potential application of this immunosuppressor in therapeutic intervention in several conditions that involve CD4 T cells.

Representative publications:

A.T. Motameni, T.C. Bates, I.J. Juncadella, C. Petty, M.N. Hedrick, J. Anguita. 2005. 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.

N. Ramamoorthi, S. Narasimhan, U. Pal, F. Bao, X.F. Yang, D. Fish, J. Anguita, M.V. Norgard, F.S. Kantor, J.F. Anderson, R.A. Koski, E. Fikrig. 2005. The Lyme disease agent exploits a tick protein to infect the mammalian host. Nature. 436:573-577.

A. Rasley, I. Marriott, C.R. Halberstadt, K.L. Bost, J. Anguita. 2004. Substance P augments Borrelia burgdorferi induced PGE2 production by murine microglia. The Journal of Immunology. 172:5707-5713.

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.

J. Anguita, M.N. Hedrick, E. Fikrig. 2003. Adaptation of Borrelia burgdorferi in the tick and the mammalian host. FEMS Microbiology Reviews. 27:493-504.

J. Anguita, S. Samanta, S. K. Ananthanarayanan, B. Revilla, G. P. Geba, S. W. Barthold, E. Fikrig. 2002 Cyclooxygenase 2 activity modulates the severity of murine Lyme arthritis. FEMS Immunology and Medical Microbiology. 34:187-191.

L. Alexopoulou, V. Thomas, M Schnare, Y. Lobet, J. Anguita, R. T. Schoen, R. Medzhitov, E. Fikrig, R. A. Flavell. 2002. Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans, TLR1- and TLR2-deficient mice. Nature Medicine. 8:878-884.

A. Rasley, J. Anguita, I. Marriott. 2002. Borrelia burgdorferi induces inflammatory mediator production by murine microglia. The Journal of Neuroimmunology. 130:22-31.

S. Diehl, C. Wong, L. Weiss, A. Palmetshofer, T. Twardzik, L. Rounds, E. Serfling, R.J. Davis, J. Anguita, M. Rincón. 2002. Induction of NFATc2 expression by IL-6 promotes Th2 differentiation. Journal of Experimental Medicine. 196:39-49.

J. Anguita*, N. Ramamoorthi* (equal contribution), J.W.R. Hovius, S. Das, V. Thomas, R. Persinski, D. Conze, P.W. Askenase, M. Rincón, F.S. Kantor, E. Fikrig. 2002. Salp15, an Ixodes scapularis salivary protein, inhibits CD4+ T cell activation. Immunity. 16:849-859.

J. Anguita, S. W. Barthold, R. Persinski, M.N. Hedrick, C.A. Huy, R.J. Davis, R.A. Flavell and E. Fikrig. 2002. Murine Lyme arthritis development mediated by p38 Mitogen Activated Protein Kinase activity. The Journal of Immunology. 168:6352-6357.