in human defense
Viral and Cellular Immunology
The interactions of the immune system and an invading viral pathogen are complex. Evidence developed in our laboratory and others implicates innate immune responses to the virus as not only providing a critical first-line defense against human viral infection, but also for directing the nature of the subsequent adaptive response. We have described a unique population of dendritic cells, the human peripheral blood plasmacytoid dendritic cells (PDC), that are the primary cells that respond to viral infection with vigorous production of interferon-?. Current studies focus on the molecular and cellular mechanisms of IFN induction including transcription factors, receptor-ligand interactions, signal transduction, cell-cell interactions between PDC and other cells types (e.g. other DC, NK cells, T cells). The interactions of these populations are being studied at the cellular and molecular levels using techniques such as multi-color flow cytometry, cytolytic assays, real time PCR, immunohistochemistry, microarrays and viral mutagenesis. Other studies in the laboratory focus on the application of the basic biology studies to clinical areas including studies of PDC and IFN dysregulation in patients with HIV infection, primary immunodeficiencies, chronic fatigue syndrome and severe viral infections.
Payvandi, F., Amrute, S., and Fitzgerald-Bocarsly, P. Exogenous and endogenous IL10 regulate inferferon-alpha production by PBMC in response to viral stimulation, J. Immunology, 160:5868, 1998.
Milone, M., and Fitzgerald-Bocarsly, P. The Macrophage mannose mediates induction of IFN-?
in peripheral blood dendritic cells by enveloped RNA and DNA viruses, J. Immunology, 161:2391-2399, 1998.
Siegal, F.P., Kadowski, N., Shodell, M., Fitzgerald-Bocarsly, P., Shah, K., Ho, S., Antonenko, S., and Liu, Y-J. The nature of the principal type 1 interferon-producing cells in human blood. Science, 284:1835-1837, 1999.
Feldman, S., Stein, D., Amrute, S., Denny, T., Garcia, Z., Kloser, P., Sun, W., and Fitzgerald-Bocarsly, P. Decreased IFN-alpha production in HIV infected patients correlates with numerical and functional deficiencies in circulating type 2 dendritic cell precursors. Clinical Immunology, 101:201-210, 2001.
Fitzgerald-Bocarsly, P. Plasmacytoid dendritic cells, the natural interferon alpha producing cells. BioTechniques, S16-S29, 2002
Izaguirre, A., Barnes, B.J., Amrute, S., Yeow, W.S., Megjugorac, N., Dai, J.H., Feng, D., Chung, E., Pitha, P.M., and Fitzgerald-Bocarsly, P. Comparative analysis of IRF-alpha expression in human plasmacytoid and monocyte-derived blood mononuclear dendritic cells. J. Leukoc Biol., 74:1125-1138, 2003.
Ryan, L.K., Diamond, G., Amrute, S., Feng, Z., Weinberg, A., and Fitzgerald-Bocarsly, P. Detection
of HBD1 peptide in peripheral blood mononuclear cell subpopulations by intracellular flow cytometry. Peptides, 24:1785-1794, 2003.
Megjugorac, N.J., Young, H.A., Amrute, S.B., Olshalsky, S.L., and Fitzgerald-Bocarsly, P. Virally stimulated plasmacytoid dendritic cells produce chemokines and induce migration of T and NK cells. J. Leukoc., Biol. 75:504-514, 2004.
Dai, J., Megjugorac, N., Amrute, S. and Fitzgerald-Bocarsly, P. Regulation of IRF-7 and IFN- a production by enveloped virus and LPS in human plasmacytoid dendritic cells. J. Immunol. , 173:1535-1548, 2004.