Lucero, Carissa
(2013)
Effects of SIV Infection on Lymphoid Chemokine CXCL13, Paneth cell Phenotype, and Intestinal Antimicrobial Peptide Expression.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
To date, the complex nature of the host’s response to the human immunodeficiency virus still intensely studied. Amongst the contributing factors to the host responses are chemokines. Attention to the role of homeostatic chemokines in HIV-1 infection has been concentrated on changes in their constitutive expression. There is evidence that demonstrates the expession levels of CXCL9 and CXCL13 are increased during infection. CXCL13 is a homeostatic, constitutively expressed chemokine responsible for the migration of lymphocytes into the germinal centers of lymphoid tissues. I examined the levels and locations of CXCL13, amongst other homeostatic chemokines, and local cell populations by detailed in situ methods in macaque lymphoid and intestinal tissues. My results indicate that there were distinct localization patterns of CXCL13 mRNA compared to protein in germinal centers. These patterns shifted during the course of SIV infection, with increased mRNA expression within and around follicles during AIDS compared to uninfected or acutely infected animals. Unexpectedly, CXCL13 expression was also found in abundance in Paneth cells in crypts throughout the small intestine. In the gastrointestinal tract, Paneth cells produce antimicrobial peptides as an innate immune mechanism to protect the epithelium from pathogenic infection. Therefore, I expanded my analyses to include Paneth cells, and chemokines and antimicrobial peptides not previously demonstrated to be expressed by Paneth cells in intestinal tissues. I examined the expression patterns of multiple chemokines including CCL25, as well as antimicrobial peptides including α-defensins 6, β-defensin 2, rhesus θ-defensin 1, and Reg3γ. Additionally, I evaluated other Paneth cell-associated factors in situ in cynomolgous macaque intestinal tissues. Results showed that no other chemokines were expressed by Paneth cells, making CXCL13 unique among the group. DEFA1, BDEF2, RTD-1, and Reg3γ expression was also clearly in Paneth cells and localized to the same cellular compartment as CXCL13 and DEFA6. These peptides have not been shown previously to be expressed by Paneth cells. I also found that during SIV infection there are differences in the expression levels of several antimicrobial peptides. These findings are of public health importance because they expand our understanding of mucosal immunology, innate antimicrobial defenses, homeostatic chemokine function, and host protective mechanisms against microbial translocation.
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| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
27 June 2013 |
| Date Type: |
Publication |
| Defense Date: |
10 April 2013 |
| Approval Date: |
27 June 2013 |
| Submission Date: |
22 April 2013 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
126 |
| 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: |
CXCL13 chemokine antimicrobial peptides SIV Paneth cells |
| Date Deposited: |
27 Jun 2013 18:13 |
| Last Modified: |
15 Nov 2016 14:12 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/18557 |
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