Faculty

Todd A. Reinhart, ScD Associate Professor, Assistant Chairman, and Director of IDM Graduate Programs E-mail: reinhar@pitt.edu Phone: 412-648-2341 Fax: 412-624-4873 Address: 606 Parran Hall 130 DeSoto Street Pittsburgh, PA 15261

Education

BA; Hamline University; 1986
ScD; Harvard University; School of Public Health, 1992

Research Interests

Role of chemokines in the pathogenesis of HIV-1 and SIV; basic biology of chemokines; immunopathogenesis of Mycobacterium tuberculosis; roles played by lymphatic endothelial cells in infectious diseases and vaccines; emerging infections and biodefense.

Research Summary

How HIV-1 causes AIDS remains incompletely understood.  We are examining the contributions of the host response during infection to better understand the changes occurring in tissues, which should in turn help to develop strategies to reverse or overcome those changes associated with pathogenesis.  Chemokines are small cytokines that recruit cells with the appropriate receptors into local environments, and they play multiple roles in the pathogenesis of HIV-1 and its nonhuman counterpart, simian immunodeficiency virus (SIV).  Our efforts are heavily focused on understanding chemokines and their contributions to infectious diseases.  Through gene expression profiling and histologic approaches, we are defining the effects of SIV on the networks of chemokines in lymphoid tissues, where much of the virus in the body is replicating.  We are finding that those chemokines that change in expression are intimately involved in shaping local immune environments that can be advantageous to the virus. 

Given the new roles we are defining for chemokines in HIV-1/SIV pathogenesis, we are also studying basic aspects of chemokine biology that could be responsible for their contributions to disease induction. 

The lymphatics drain extracellular fluids and cells from peripheral tissues to lymph nodes and then ultimately into the blood stream.  A new direction in the laboratory is focusing on the role that lymphatic endothelial cells (LECs) might play in inflammatory responses to infections, including those by HIV-1/SIV and Mycobacterium tuberculosis.  Our studies to date indicate that there are multiple types of LECs in peripheral tissues and lymph nodes and they are exquisitely poised to sense and respond to pathogens.  We are currently exploring their possible contribution to the formation and maintenance of inflammatory structures surrounding M. tuberculosis infectious foci called granulomas. 

In the areas of emerging infections and biodefense, we are participating in a new project that seeks to develop a DNA vaccine for seasonal and pandemic influenza and have begun a new collaborative project to determine the effects of anthrax toxins expressed by Bacillis anthracis on the immune and other organ systems. 

Recent Publications

• Sanghavi, S.K., R. Shankarappa, and T.A. Reinhart. (2004) Analysis of Toll/Interleukin-1 receptor (TIR) domain sequences from rhesus macaque TLRs 1-10 identifies species-specific differences within otherwise highly conserved innate immune signaling domains.  Immunogenetics 56:667-674.
• Sanghavi, S.K. and T.A. Reinhart. (2005) Increased Expression of Toll-like Receptor 3 in Lymph Nodes during Simian Immunodeficiency Virus Infection:  Implications for Inflammation and Immunodeficiency.  Journal of Immunology 175:5314-5323.
• Schaefer, T.M., C.L. Fuller, S. Basu, B.A. Fallert, S.L. Poveda, S.K. Sanghavi, Y.-K. Choi, D.E. Kirschner, E. Feingold, and T.A. Reinhart. (2006) Increased Expression of Interferon-inducible Genes in Macaque Lung Tissues during SIV Infection.  Microbes and Infection 8:1839-1850. 
• Lin, P.L., S. Pawar, A. Myers, A. Pegu, C. Fuhrman, T.A. Reinhart, S.V. Capuano, E. Klein, J.L. Flynn.  (2006) Early events in Mycobacterium tuberculosis infection in cynomolgus macaques.  Infection and Immunity 74:3790-3803. 
• Rappocciolo, G., P. Piazza, C.L. Fuller, T.A. Reinhart, S.C. Watkins, D.T. Rowe, M. Jais, A. Hoji, P. Gupta, and C.R. Rinaldo.  (2006) B Lymphocytes Express DC-SIGN and Transmit HIV-1 to T Lymphocytes.  PLoS Pathogen 2(7):e70; 0691-0704.
• Pegu, A., J.L. Flynn, and T.A. Reinhart.   (2007)  Afferent and Efferent Interfaces of Lymph Nodes Are Distinguished by Expression of Lymphatic Endothelial Markers and Chemokines.  Lymphatic Research and Biology, 5(2):91-104.
• Clay, C.C., D.S. Rodrigues, Y.S. Ho, B.A. Fallert, K. Janatpour, T.A. Reinhart, and U. Esser.  (2007) CNS Inflammation And Acute Neuroinvasion of Fluorescein+ Monocytes in The Nonhuman Primate Animal Model for AIDS.  Journal of Virology 81(21):12040-12048. 
• Fallert, B.A., S. Poveda, T.M Schaefer, M.E. Pfeifer, S.K. Sanghavi, S.C. Watkins, M.A. Murphey-Corb, P.M. Tarwater, D.E. Kirschner, and T.A. Reinhart.  (2008)  Virologic and Immunologic Events in Hilar Lymph Nodes During Simian Immunodeficiency Virus Infection:  Development of Polarized Inflammation.  Journal of the Acquired Immune Deficiency Syndromes 47(1):16-26. 
• Pegu, A., S. Qin, B.A. Fallert Junecko, R.E. Nisato, M.S. Pepper, and T.A. Reinhart.  (2008) Human Lymphatic Endothelial Cells Express Multiple Functional Toll-like Receptors.  Journal of Immunology 180(5):3399-3405. 
• Aujla, S.J., M. Fei, D.A. Pociask, T.A. Reinhart, J. Edeal, K. Gaus, J.L. Kreindler, P.J. Dubin, M. Zheng, J.M. Pilewski, M.M. Myerburg, C.A. Mason, Y. Iwakura, and J. Kolls.  (2008) IL-22 Mediates Mucosal Host Defense against Gram Negative Bacterial Pneumonia.  Nature Medicine 14(3):275-81. 
• Rappocciolo, G.R., H.H. Hensler, M. Jais, T.A. Reinhart, A. Pegu, F.J. Jenkins, and C.R. Rinaldo.  (2008) HHV-8 Infects and Replicates in Primary Cultures of Activated B Lymphocytes through DC-SIGN.  Journal of Virology, in press.

• Qin†, S., Y. Sui†, A. Soloff, B.A.F. Junecko, S.C. Watkins, D.E. Kirschner, J.E. Pease, M.A. Murphey-Corb, S. Barratt-Boyes, and T.A. Reinhart.  (2008)  Chemokine and Cytokine Mediated Loss of Regulatory T cells in Lymphoid Tissues during Pathogenic Simian Immunodeficiency Virus Infection.  †These authors contributed equally to this work.  Journal of Immunology, in press.

Dr. Reinhart's Lab

Front row: Beth Fallert, Carissa Flores, Yongjun Suit
Back row: Dr. Todd Reinhart, Shulin Qin, Cynthia Klamar