Todd A. Reinhart, ScD
606 Parran Hall
130 DeSoto Street
Pittsburgh, PA 15261
BA; Hamline University; 1986
ScD; Harvard University; School of Public Health, 1992
Role of chemokines in the pathogenesis of HIV-1 and SIV; basic biology and inhibition of chemokines; roles played by lymphatic endothelial cells in infectious diseases and vaccines; vaccines for HIV-1, influenza, and cancer.
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 primate 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. Similarly, we are contributing to a large collaborative effort to determine how chemokines contribute to tumor-specific T cells trafficking and treatment of cancers.
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 in infectious diseases as well as other chronic inflammatory diseases.
The lymphatics drain extracellular fluids and cells from peripheral tissues to lymph nodes and then ultimately into the blood stream. One focus we have is on the role that lymphatic endothelial cells (LECs) might play in inflammatory responses to infections, including those by HIV-1/SIV. 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 exploring whether LECs could be playing roles in HIV/SIV pathogenesis and transmission.
Selected Recent Publications
Qin, S, BA Fallert Junecko, AM Trichel, PM Tarwater, MA Murphey-Corb, DE Kirschner, and TA Reinhart. (2010) Simian Immunodeficiency Virus Infection Alters Chemokine Networks in Lung Tissues of Cynomolgus Macaques: Association with Pneumocystis carinii infection. American Journal of Pathology 177(3):1274-85.
Qin, S, JF Alcorn, JK Craigo, C Tjoeng, Patrick M Tarwater JK Kolls, and TA Reinhart. (2011) Epigallocatechin-3-Gallate Reduces Airway Inflammation in Mice through Binding to Proinflammatory Chemokines and Inhibiting Inflammatory Cell Recruitment. Journal of Immunology 186(6):3693-700.
Khader, SA, L Guglani, J Rangel-Moreno, R Gopal, BA Fallert Junecko, JJ Fountain, C Martino, JE Pearl, M Tighe, YY Lin, S Slight, JK Kolls, TA Reinhart, TD Randall, and AM Cooper. (2011) IL-23 is required for long-term control of Mycobacterium tuberculosis and B cell follicle formation in the infected lung. Journal of Immunology 187(10):5402-7.
Guglani, L, J Rangel-Moreno, B Fallert Junecko, R Gopal, Y Lin, J Alcorn, EV Scheller, T Berger, TW Mak, J Kolls, T Randall, TA Reinhart, Y Chan, and S Khader. (2013) Lipocalin 2 Regulates Chemokines and Inflammation During Pulmonary Mycobacterial Infections. PLoS One, in press.
Slight, SR, J Rangel-Moreno, Y Lin, R Gopal, BA Fallert Junecko, M Selman, D Kaushal, J Baquera-Heredia, E Becerril-Villanueva, L Pavon-Romero, GM Winslow, DL Woodland, TA Reinhart, TD Randall, SA Khader. (2013) CXCR5+ expression on T helper cells mediates protective immunity against tuberculosis. Journal of Clinical Investigation, in press.
Choi, S-M, JP McAleer, M Zheng, DA Pociask, MH Kaplan, S Qin, TA Reinhart, and JK Kolls. (2013) Innate STAT3-mediated induction of antimicrobial protein, Reg3g is required for host defense against MRSA pneumonia. Journal of Experimental Medicine, in press.
Gopal, R, J Rangel-Moreno, Y Lin, S Slight, H Nawar, BA Fallert Junecko, TA Reinhart, J Kolls, T Randall, T Connell, and S Khader. (2013) Interleukin-17-dependent CXCL-13 mediates mucosal vaccine-induced immunity against tuberculosis. Mucosal Immunology, in press.
Choi, YK, BA Fallert Junecko, CR Klamar, and TA Reinhart. (2013) Distribution and Characterization of Cells Expressing Lymphatic Marker LYVE-1 in Macaque Intestine during Simian Immunodeficiency Virus Infection. Lymphatic Research and Biology, in press.
Qin, S, CR Klamar, BA Fallert Junecko, J Craigo, DH Fuller, and TA Reinhart. (2032) Functional Characterization of Ferret CCL20 and CCR6 and Identification of Chemotactic Inhibitors. Cytokine, in press.
Founds, SA, BA Fallert Junecko, TA Reinhart, and WT Parks. (2013) LAIR2-Expressing Extravillous Trophoblasts Associate with Maternal Spiral Arterioles Undergoing Physiologic Conversion. Placenta, in press.
Dr. Reinhart's Lab