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Simon Barratt-Boyes, BVSc, PhD, DACVIM

Professor, Infectious Diseases and Microbiology

Member, Center for Vaccine Research

Professor, Immunology

Contact

9046 BST3, Center for Vaccine Research, 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.

Acute lung injury in H5N1 influenza: Highly pathogenic avian influenza viruses including H5N1 and H7N9 strains cause severe pneumonia and acute respiratory distress syndrome in humans, and infections are often fatal. Our understanding of the pathogenesis of infection and how we might best prevent severe disease are hampered by the lack of a large animal model that truly reproduces human illness. We have overcome this significant problem by developing an aerosol challenge model of H5N1 influenza virus infection in nonhuman primates, working in the University of Pittsburgh’s Regional Biocontainment Laboratory. Aerosolization delivers virus to the lower respiratory tract and induces acute respiratory distress syndrome in macaques. With this model we can now test novel strategies targeting the over-exuberant innate immune response to prevent acute lung injury. These new therapeutic approaches could prevent the tens of thousands of influenza deaths each year and could be used as the first line of defense to contain an influenza pandemic.

Dengue and Zika virus infection in human skin: Dengue is the most important insect-borne viral disease of humans worldwide and is expanding rapidly on a global scale. The Zika epidemic in the Americas in 2015-16 caused microcephaly and other serious congenital defects, and Zika infections continue at a low level in Brazil today. Both viruses are transmitted via the skin, but the early events that take place following inoculation into skin are poorly understood. We have addressed this problem by developing an ex vivo model of dengue and Zika virus infection in human skin explants. We have recently shown that keratinocytes are a major target of dengue virus infection, and that innate responses by infected keratinocytes lead to recruitment of virus-permissive myeloid cells including dendritic cells and macrophages that serve to expand infection and disseminate virus out of skin. We have now developed the first model of antibody-dependent enhancement of dengue and Zika virus infection in human skin. This new model will allow us to understand how immunity to one virus induced either by infection or vaccination impacts infection with a second virus, be it dengue or Zika.

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 have defined DC populations in the macaque model and studied the trafficking of ex vivo propagated DC after injection into donor animals. Using specific inhibitors of TLR7 and TLR9, we showed 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. 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 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.


Education

1984 | Massey University, Palmerston North, New Zealand | Bachelor of Veterinary Science
1993 | University of California, Davis | PhD

1996 | University of Pittsburgh | Postdoc


Teaching

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


Selected Publications

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. J Immunol; 190: 80-87.

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(12): 2012-2016  

 

Wonderlich ER, Wen-Chi Wu, Normolle DP, 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: 446-454. (Cover art).

 

Wonderlich ER, Swan ZD, Bissel SJ, Hartman AL, Carney JP, O’Malley KJ, Obadan AO, Santos J, Walker R, Sturgeon TJ, Frye LJ Jr., Maiello P, Scanga CA, Bowling JD, Bouwer AL, Duangkhae PA, Wiley CA, Flynn JL, Wang J, Cole KS, Perez DR, Barratt-Boyes SM. (2017). Widespread virus replication in alveoli drives acute respiratory distress syndrome in aerosolized H5N1 influenza infection of macaques. J Immunol; 198: 1616-1626.

 

Swan ZD, Bouwer AL, Wonderlich ER, Barratt-Boyes SM.  (2017).  Persistent accumulation of gut macrophages with impaired phagocyte function correlates with SIV disease progression in macaques.  Eur J Immunol; 47:1925-1935.

Duangkhae P, Erdos G, Ryman KD, Watkins SC, Falo LD Jr, Marques ETA Jr, Barratt-Boyes SM.  (2017).  Interplay between keratinocytes and myeloid cells drives dengue virus spread in human skin.  J Invest Dermatol.

 

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: 446-454. (Cover art).

 

Wonderlich ER, Swan ZD, Bissel SJ, Hartman AL, Carney JP, O’Malley KJ, Obadan AO, Santos J, Walker R, Sturgeon TJ, Frye LJ Jr., Maiello P, Scanga CA, Bowling JD, Bouwer AL, Duangkhae PA, Wiley CA, Flynn JL, Wang J, Cole KS, Perez DR & Barratt-Boyes SM. (2017). Widespread virus replication in alveoli drives acute respiratory distress syndrome in aerosolized H5N1 influenza infection of macaques. J Immunol; 198: 1616-1626.

 

Swan ZD, Bouwer AL, Wonderlich ER & Barratt-Boyes SM (2017). Persistent accumulation of gut macrophages with impaired phagocytic function correlates with SIV disease progression in macaques. Eur J Immunol; 47: 1925-1935.

 

Duangkhae P, Erdos G, Ryman KD, Watkins SC, Falo LD Jr., Marques ETA Jr. & Barratt-Boyes SM (2018). Interplay between keratinocytes and myeloid cells drives dengue virus spread in human skin. J Invest Dermatol; 138: 618-626.

Simon  Barratt-Boyes
© 2018 by University of Pittsburgh Graduate School of Public Health

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