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Evaluation of dengue virus infection in immune cells of human skin

Smith, Amanda Paige (2010) Evaluation of dengue virus infection in immune cells of human skin. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Dengue virus (DENV) is a reemerging infectious agent causing an estimated 50-100 million cases annually and is endemic in more than 100 countries. Recently there has been an increase in the geographic spread, the overall number, and the severity of disease cases, making DENV an increasing threat to public health. The most prevalent of the arboviruses, DENV is introduced into human hosts during a vector mosquito's blood meal; here, virus is deposited into the epidermal and dermal layers of the skin. Therefore, elucidating the cutaneous immune response to DENV is critical to our understanding of the immune mechanisms involved in protection and pathogenesis of DENV and to the development of effective treatments and vaccines. In addition to resident T- and B-cells, the skin immune system includes three major populations of innate immune cells, dermal dendritic cells (dDCs), dermal macrophages (dMØs), and epidermal Langerhans' cells (LCs). These immune cells are potential targets of DENV infection. The receptor profile of dDCs and dMØs indicates that they are susceptible to DENV infection, however evidence of this is lacking. LCs are infected following ex vivo inoculation of human skin explants, yet their role in DENV pathogenesis remains unclear. Upon exposure to a pathogen, cutaneous immune cells mature and migrate to the cutaneous draining lymph node via the draining lymphatics; these functions are critical to the induction of adaptive immune responses and to pathogen clearance. It remains unclear how DENV infection affects the maturation, migration and survival of cutaneous immune cells. Herein, we use a combination of in vitro studies and ex vivo inoculation of healthy human skin explants to explore the role of cutaneous immune cells in DENV infection. We investigated the degree to which cutaneous immune cells become infected with DENV and measured upregulation of activation markers, migration out of the skin, and the life span of infected cells. We discovered that populations of cutaneous DCs, as well as dMØs, become infected with DENV upon scarification of skin with virus. In vitro, we confirmed that DENV infection partially inhibits maturation of DCs and potentially MØs. Additionally, DENV infection induces DC apoptosis in a caspase-dependent manner. These results help to clarify the role of cutaneous immune cells in the immunopathogenesis of DENV.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Smith, Amanda Paigeasmithp@gmail.com
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairBarratt-Boyes, Simon Msmbb@cvr.pitt.eduSMBB
Committee MemberRinaldo, Charles Rrinaldo@pitt.eduRINALDO
Committee MemberMarques, Ernesto T.Amarques@cvr.pitt.eduMARQUES
Date: 27 September 2010
Date Type: Completion
Defense Date: 26 July 2010
Approval Date: 27 September 2010
Submission Date: 26 July 2010
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: cutaneous; dendritic cell; dengue; dengue virus; dermal; epidermal; keratinocyte; skin; macrophage; skin immune system
Other ID: http://etd.library.pitt.edu/ETD/available/etd-07262010-184854/, etd-07262010-184854
Date Deposited: 10 Nov 2011 19:54
Last Modified: 15 Nov 2016 13:47
URI: http://d-scholarship.pitt.edu/id/eprint/8633

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