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Simon Barratt-Boyes, BVSc, PhD

Professor, Infectious Diseases and Microbiology

Member, Center for Vaccine Research

Contact

9046 BST3, 3501 Fifth Avenue, Pittsburgh, PA 15260
R-znvy: fzoo@cvgg.rqh
Primary Phone: 967-838-2082


Personal Statement

Research in the Barratt-Boyes laboratory addresses the immunology of infectious diseases of importance to humans. There are three major areas of interest.

Dendritic cells and macrophages in simian immunodeficiency virus (SIV) infection of nonhuman primates: The laboratory addresses the relationship between dendritic cells (DC) and macrophages and progression or control of SIV infection in the rhesus macaque model. We also have a long-standing interest in using DC as vaccine vehicles for SIV and HIV, given their capacity as superior antigen-presenting cells. We have defined DC populations in the macaque model and studied the trafficking of ex vivo propagated DC after injection into donor animals. We showed that activated plasmacytoid DC are recruited to and undergo apoptosis in lymphoid tissues resulting in depletion in acute infection. Plasmacytoid dendritic cells recognize and respond to viruses by producing copious amounts of type I interferon (IFN). Using specific inhibitors of TLR7 and TLR9, we showed that that plasmacytoid DC contribute the majority of type I IFN produced in lymph nodes during acute SIV infection, but that this response does not drive immune activation during early SIV infection. We have also found that myeloid DC in SIV infected monkeys produce cytokines in response to virus-encoded TLR ligands but that tissue myeloid DC and macrophages lose the capacity to stimulate T cells in SIV infection associated with reduced production of IL-12 and IFN-α. We have recently found that macrophages accumulate in the gut mucosa in monkeys with AIDS but are not present in such large numbers in these tissues in chronic infection without disease. Our current efforts are aimed at defining the function of these macrophages. We are also pursuing ways of using the potency of ex vivo-generated DC as therapeutic vaccines in a curative strategy for HIV infection using the SIV model.  

Highly pathogenic avian influenza virus infection in nonhuman primates: The association of severe human disease with markedly increased proinflammatory cytokines and macrophage infiltration into lungs during H5N1 influenza virus infection suggests that innate immune dysregulation may contribute to disease pathogenesis, but surprisingly little is known about the mechanism of disease in humans. This represents a critical gap in knowledge, as understanding the process of severe disease is essential to developing therapeutic approaches to control disease should a pandemic outbreak occur. Nonhuman primates represent an attractive model for studying H5N1 infection and pathogenesis, and we are developing this model in studies using the Regional Biocontainment Laboratory of the University of Pittsburgh, which provides high-containment facilities for working with H5N1 viruses in large animals.

Targets of dengue virus infection in humans: Dengue is the most important insect-borne viral disease of humans worldwide and is expanding rapidly on a global scale. Dengue is most often a debilitating but self-limiting illness; however a significant fraction of dengue virus-infected individuals experience a life-threatening disease known as dengue hemorrhagic fever characterized by severe plasma leakage. The pathogenesis of dengue and the reason why some individuals develop severe disease are poorly understood, although it is known that increased disease severity is associated with secondary infections and the presence of infection-enhancing antibodies. In collaboration with researchers at the University of Pittsburgh and Fiocruz in Brazil we showed that acute dengue virus infection is associated with significant increases in the frequency of plasmablasts, which are antibody-secreting cells found in the circulation. Importantly, we found that the magnitude of the virus-specific plasmablast response was associated with increased severity of dengue disease in patients with secondary infection, with up to 90% of circulating B cells being plasmablasts in some individuals. In other work we are defining the targets of dengue virus infection in human skin using explants from elective plastic surgery procedures. This work is aimed at determining the predominant cell type to be infected and whether the innate response to infection promotes or prevents virus spread within skin.  


Education

1984 | Massey University, Palmerston North, New Zealand | Bachelor of Veterinary Science
1991 | American College of Veterinary Internal Medicine | Diplomate
1993 | University of California, Davis, CA | Doctor of Philosophy


Teaching

Co-Director | IDM 2003 | Host Response to Microbial Infection


Selected Publications

Wonderlich ER & Barratt-Boyes SM (2012) A dendrite in every pie: Myeloid dendritic cells in HIV and SIV infection. Virulence; 3: 647-653.

 

Garcia-Bates TM, Cordeiro MT, Nascimento EJM, Smith AP, Soares de Melo KM, McBurney SP, Evans JD, Marques ETA Jr & Barratt-Boyes SM (2013) Association between magnitude of the virus-specific plasmablast response and disease severity in dengue patients. Journal of 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 simian immunodeficiency virus infection. Journal of Immunology; 190 (5):2188-2198.

 

Kader M, Smith AP, Guiducci C, Wonderlich ER, Normolle D, Watkins SC, Barrat FJ, Barratt-Boyes SM (2013)  Blocking TLR7 and TLR9 mediated IFN-α production by plasmacytoid dendritic cells does not diminish immune activation in early SIV infection. PLoS Pathogens; 9: e1003530.

 

Soloff AC, Bissel SJ, Giles BM, Ross TM & Barratt-Boyes SM (2014)  Massive mobilization of plasmacytoid and myeloid dendritic cells in H5N1 influenza virus infection of nonhuman primates. J Inf Dis; 209: 2012-2016

 

Nascimento EJM, Hottz ED, Garcia-Bates TM, Bozza F, Marques ETA Jr & Barratt-Boyes SM, (2014)  Emerging concepts in dengue pathogenesis: Interplay between plasmablasts, platelets and complement in triggering vasculopathy. Crit Rev Immunol; 34: 227-240.

 

Wonderlich ER, Wu W-C, Normolle D & Barratt-Boyes SM (2015)  Macrophages and myeloid dendritic cells lose T-cell stimulating function in simian immunodeficiency virus infection associated with diminished IL-12 and IFN-α production. J Immunol; 195: 3284-3292.

 

Swan ZD, Wonderlich ER & Barratt-Boyes SM (2016)  Macrophage accumulation in gut mucosa differentiates AIDS from chronic SIV infection in rhesus macaques. Eur J Immunol; 46: 446-54. [Journal cover image]

 


Simon  Barratt-Boyes
© 2017 by University of Pittsburgh Graduate School of Public Health

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