Berendam, Stella J
(2015)
Innate immune potential of primary lymphatic endothelial cells.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Lymphatic endothelial cells (LECs) are loosely overlapping cells that line the lymphatic vasculature. In tissues, LECs are often located directly beneath the mucosal epithelial layer, and therefore, are likely to be among the first cells that come in contact with incoming pathogens and/or vaccine antigens and adjuvants when there is a breakage at the epithelial barrier. We are only starting to appreciate the role of LECs in the development of host innate and adaptive immune responses during infection or vaccine administration. This is largely due to the difficulties in studying LECs in vivo and the challenges in obtaining pure LEC cultures for study ex vivo. My work focused on isolation and establishment of primary LEC cultures derived from different tissue origins of commonly used animal models – ferrets and rhesus macaques – and assessment of the potential of these LECs to respond to pathogen-associated molecular patterns (PAMPs) or a subset of microbes (SIV/HIV-1). In addition, I also partially compared the phenotype and functionality of LECs to dendritic cells (DCs), an immune cell type that acts as a “bridge” between the host innate and adaptive immunity. My findings revealed that LECs were highly heterogeneous in their gene expression profiles. They also endogenously expressed multiple known viral entry and restriction factors for SIV/HIV-1. LECs responded to several PAMPs by producing proinflammatory cytokines/chemokines that are known to recruit immune cells to sites of inflammation. However, LECs were not highly susceptible or permissible to infection using genetically engineered, single-cycle competent SIV/HIV-1 or wild-type SIV. Interestingly, LECs expressed phenotypic markers that have been shown to be expressed by DCs and showed some functional similarities. LECs were able to take up and process model antigens, although it was not determined if these antigens were presented by MHC I and II molecules. These findings are of public health importance because they expand our knowledge of the emerging potential of LECs as key players in innate immunity during pathogen-host interactions or vaccinations. Improving our understanding of LECs will positively impact our knowledge of mucosal infections and will help in development of improved treatment and vaccination strategies. These primary cells will serve as tools to study LEC immunobiology and will also be useful in development of vaccines/therapeutics for human diseases of public health importance that target LEC and/or its crosstalk with other immune cells.
Share
| Citation/Export: |
|
| Social Networking: |
|
Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
29 June 2015 |
| Date Type: |
Publication |
| Defense Date: |
13 April 2015 |
| Approval Date: |
29 June 2015 |
| Submission Date: |
7 April 2015 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
200 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Infectious Diseases and Microbiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
lymphatic |
| Date Deposited: |
29 Jun 2015 14:57 |
| Last Modified: |
19 Dec 2016 14:42 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/24630 |
Metrics
Monthly Views for the past 3 years
Plum Analytics
Actions (login required)
 |
View Item |
![[img]](https://d-scholarship.pitt.edu/style/images/fileicons/application_pdf.png)
![[feed]](/images/feed-icon-32x32.png){kind=icon}