Simon M. Barratt-Boyes, BVSc, PhD
Professor, Department of Infectious Diseases and Microbiology and Department of Immunology, School of Medicine (Secondary Appointment)
Center for Vaccine Research
3501 Fifth Avenue
Pittsburgh, PA 15260
BVSc; Massey University, New Zealand; 1984
PhD; University of California, Davis; 1993
Viral immunology and pathogenesis
Our research addresses the immunology of infectious diseases of importance to humans. We have three major projects in the laboratory at present.
Mononuclear phagocytes in simian immunodeficiency virus (SIV) infection Mononuclear phagocytes are important innate immune cells that include monocytes, macrophages, and dendritic cells, which in the human and nonhuman primate consist of two major subsets, myeloid and plasmacytoid. Given their function in antiviral immunity, dendritic cells are thought to play a protective role in HIV and SIV infection, and loss of both subsets is associated with disease progression. However, recently emphasis has been placed on the potential role of the innate immune response in chronic, generalized immune activation that is a hallmark of AIDS. In this scenario, over-active mononuclear phagocytes produce pro-inflammatory cytokines that drive chronic interferon production and inflammation in lymphoid and gut tissues. Hence there is a basic unanswered question in HIV pathogenesis: are dendritic cells, monocytes and macrophages beneficial or detrimental to the infected host? We use the model of SIV infection of rhesus macaques, which replicates the pathogenesis of HIV-1 infection in humans and leads to simian AIDS, to address this question.
Dendritic cell responses in influenza virus infection Influenza virus is a respiratory pathogen that targets the lung, and innate immune responses serve a key role in providing early antiviral immunity and limiting disease in acute infection. However, the relationship between dendritic cells and immunity in the lung is not well defined. We have used the murine model to examine the impact of plasmacytoid dendritic cells in the early immune response to influenza virus infection. We are also studying the dynamics of the dendritic cell response to avian influenza virus infection in the lung of nonhuman primates, which serves as a more robust model of influenza in humans than does the mouse.
B cells in the immunity and pathogenesis of dengue Dengue is an emerging pathogen of humans that has become a major global public health concern. Dengue virus infection can manifest as either a self-limiting febrile illness or a fulminant systemic disease with plasma leakage and death. The factors that contribute to these divergent outcomes are not well defined. Antibodies have been linked to the pathogenesis of severe dengue, but little is known about the response of B cells themselves. To address this gap in knowledge, we have begun to study the plasmablast response in humans with acute dengue virus infection using a cohort of patients in Brazil.
Select Recent Publications
Garcia-Bates TM, Cordeiro MT, Nascimento EJM, Smith AP, Soares de Melo KM, McBurney SP, Evans JD, Marques ETA & Barratt-Boyes SM (2013) Association between magnitude of the virus-specific plasmablast response and disease severity in dengue patients. J Immunology; 190: 80-87.
Wonderlich ER, Wijewardana V, Liu X & Barratt-Boyes SM (2013) Virus-encoded TLR ligands reveal divergent functional responses of mononuclear phagocytes in pathogenic SIV infection. J Immunology; in press.
Soloff AC, Weirbeck HK, Ross TM & Barratt-Boyes SM (2012) Plasmacytoid dendritic cell depletion leads to enhanced mononuclear phagocyte response in lungs of mice with lethal influenza virus infection. Comparative Immunology, Microbiology and Infectious Diseases; 35: 309-317.
Wonderlich ER, Kader M, Wijewardana V & Barratt-Boyes SM (2011) Dissecting the role of dendritic cells in simian immunodeficiency virus infection and AIDS. Immunologic Research; 50: 228-234.
Wijewardana V, Soloff AC, Liu X, Brown KN & Barratt-Boyes SM (2010) Early myeloid dendritic cell dysregulation is predictive of disease progression in simian immunodeficiency virus infection. PLoS Pathogens, 6:e1001235.
Soloff AC, & Barratt-Boyes SM (2010) Enemy at the gates: Dendritic cells and immunity to mucosal pathogens. Cell Research. 20: 872-885.
Center for Vaccine Research
9052 BST3, 412-383-9057
Elizabeth R. Wonderlich, PhD – post doctoral fellow
Tatiana M. Garcia-Bates, PhD – post doctoral fellow
Zachary Swan, MS – doctoral student
Andrea K. Dobbs - MS student
Amanda Smith, MS – research technician