Nahed Ismail, MD, PhD, D(ABMM), D(ABMLI)
Associate Professor of Pathology
Dr. Ismail is a member of the Division of Clinical Microbiology at UPMC and serves as Medical Director of the Clinical Microbiology Lab at Magee-Womens Hospital of UPMC. She is board-certified by the American Board of Medical Microbiology (ABMM) and American Board of Medical Laboratory Immunology (ABMLI). She serves as Chair-Elect for Division V (Clinical and Diagnostic Immunology) of the American Society of Microbiology.
Department of Pathology
S739 Scaife Hall
3550 Terrace Street
Pittsburgh, PA 15213
Office Telephone: 412-648-8436
Lab Telephone: 412-648-8067
Fax: (412) 648-9564
Research ExpertiseDr. Ismail has a long-standing interest in understanding the immune mechanisms involved in host defense against intracellular bacteria. Her research is focused on tick-borne infections caused by ehrlichiae and rickettsiae, which cause a number of different diseases including potentially fatal human monocytic ehrlichiosis (HME) and spotted fever group rickettsiosis (SFGR).
Using murine models of human monocytic ehrlichiosis, we have discovered that fatal disease is due to immunopathology mediated by natural killer (NK) cells and CD8 T cells. These findings were unexpected, because NK and CD8 T cells are known to normally contribute to protective immunity against infections with intracellular pathogens. Although clearance of ehrlichiae is mediated by CD4+T producing IFN-gamma, these cells undergo suppression and/or apoptosis during fatal disease.
In my lab, our current research aims to analyze the immune-pathogenic mechanisms that lead to fatal human ehrlichiosis. Current projects in the lab include:
- determining how ehrlichiae activates NK and CD8 T cells
- investigating the underlying mechanism of tissue injury mediated by NK and CD8 T cells
- analyzing the role of macrophages and dendritic cells in activation and differentiation of protective CD4+Th1 cells
- determining the contributions of cytokines and chemokines, as well as their corresponding receptors, to the pathogenesis of fatal ehrlichiosis.
Several molecular and immunological technologies are utilized in Dr. Ismail's research. These include microarrays, serial analysis of gene expression, proteomic approaches, multi-parameter flow cytometry, radiation chimera, gene targeted knockout mice. In addition, the lab utilizes standard cell cultures, microbiologic, histopathologic, and confocal microscopy studies to determine mechanisms of diseases caused by these bacterial pathogens.
Studies outlined above will enable us to identify or evaluate novel host or microbial targets that can be used in the development of vaccine or immunotherapy against these important pathogens.
Selected PublicationsView Dr. Ismail's publications on PubMed
Ghose, P., A. Q. Ali, R. Fang, D. Forbes, B. Ballard, and N. Ismail (2011). The interaction between IL-18 and IL-18R limits the magnitude of protective immunity and enhances pathogenic responses following infection with intracellular bacteria. J. Immunol. 187:1333-46.
Stevenson, H.L., Estes, D.M., Thirumalapura, R. N., Walker, D.H. and Ismail, N. (2010) Natural killer cells promote tissue Injury and systemic inflammatory responses during fatal Ehrlichia-induced toxic shock-like syndrome. American Journal of Pathology, 177: 766-776. PMCID: PMC2913354
Stevenson, H.L., Walker, D.H., and Ismail, N. (2008). Regulatory role of CD1d-restricted NKT cells in the induction of toxic shock-like syndrome in an animal model of fatal ehrlichiosis. Infection and Immunity, 76:1434-44. PMCID: PMC2292873.
Thirumalapura N.R., Crossley E.C., Walker D.H., and Ismail N. (2009). Persistent infection contributes to heterologous protective immunity against fatal ehrlichiosis. Infection and Immunity, 77:5582-9. PMCID: PMC2786466.
Thirumalapura, N.R., Walker, D. H., and Ismail, N. (2008). Protective heterologous immunity against fatal ehrlichiosis and lack of protection following homologous challenge. Infection and Immunity, 76:1920-30. PMCID: PMC2346691.
Fang, R., Ismail, N., and Walker, D.H. (2009). CD4+CD25+ Foxp3-CTLA-4+ T regulatory cells are the major source of IFN-gamma and IL-10 in acute fatal rickettsial infection. Infection and Immunity, 77:3838-49. PMCID: PMC2738046.
Walker, D.H., and Ismail, N. (2008). Rickettsiosis: Emerging and re-emerging endothelial infection and early disease events. Nature Reviews Microbiology, 6:375-86. 2008. PMID: 18414502.
Fang, R., Ismail, N., Soong, L., Popov, V. L., Whitworth, T., Bouyer, D.W., and Walker, D.H. (2007) Differential interaction of dendritic cells with Rickettsia: impact on host susceptibilities to murine spotted fever rickettsiosis, Infection and Immunity 75:3112-23, 2007. PMCID: PMC1932850.
Ismail, N., Stevenson, H.L., Crossley, E.C., and Walker, D.H. (2007). The relative importance of T cell subsets in immunity and immunopathology of monocytotropic ehrlichiosis: A novel effector mechanism involved in Ehrlichia-induced immunopathology in murine ehrlichiosis. Infection and Immunity 75:4608-20. PMCID: PMC1951155.
Stevenson, H.L., Peerwani, Z., Jordan, j.M., Wang, H-Q, Walker, D.H., and Ismail, N. (2006). An intradermal environment promotes a protective type-1 response against monocytotropic Ehrlichia. Infection and Immunity 74:4856-64. PMCID: PMC1539596.
Ismail, N., Stevenson, H.L., Walker, D.H. (2006). The Role of TNF-alpha and IL-10 in the pathogenesis of severe murine monocytotropic ehrlichiosis: Increased resistance of TNF receptor p55- and p75-deficient mice to fatal ehrlichial infection. Infection and Immunity 74: 1846-56. PMCID: PMC1418656.
Ismail, N., Soong, L., McBride, J.W., Valbuena, G., Olano, J., Feng, H-M., and Walker, D.H. (2004). Overproduction of TNF alpha by CD8+ type-1 cells and downregulation of IFN-gamma production by CD4+ Th1 cells contribute to toxic shock like syndrome in an animal model of fatal monocytotropic ehrlichiosis. The Journal of Immunology 172: 1786-800. PMID: 14734762
Mattner, J., DeBord, K.L., Ismail, N., Zhou, D., Cantu, C., Mezard, P.S., Wang, V., Hoebe, K., Schneewind, O., Walker, D.H., Butler, B., Teyton, L., Savage, P.B., and Bendelac, A. (2004). Both exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature 434:525-9.
ReviewsIsmail, N. (2011). Pathogenesis of Ehrlichia and Anaplasma Infection and Disease. In Critical needs and gaps in understanding: prevention, amelioration, and resolution of lyme and other tick-borne diseases: The short-term and long-term outcomes. Workshop report, Institute of Medicine, National Academy of Science press, 114-118, 2011.
Stevenson, H. L., and N. Ismail. (2011). Innate Immune Response and Inflammation: Roles in Pathogenesis and Protection against Anaplasmataceae. ASM Text on Rickettsiales.
Ismail, N., K. C. Bloch, and J. W. McBride. (2010). Human Ehrlichiosis and Anaplasmosis. The Clinics in Laboratory Medicine, 30: 261-292.
McBride, J. W., J. Olano, and N. Ismail. (2010). Molecular diagnosis of Ehrlichia infection. Taylor & Francis Group (CRC Press), Molecular Detection of Human Bacterial Pathogens, Dongyou Liu.
Ismail, N., and M. McGinnis. (2008). Host defense and immune response to fungal infections of the skin. Clinical Immunodermatology Textbook: Anthony Gaspari & Stephen Tyring. Springer London.