Please use this identifier to cite or link to this item:
http://hdl.handle.net/11375/13312
Title: | CHARACTERIZING THE ROLE OF TOLL-LIKE RECEPTOR 2 IN SENSING AND REGULATING HUMAN IMMUNDEFICIENCY VIRUS-1 INFECTION FROM MOTHER-TO-CHILD THROUGH BREAST MILK |
Authors: | Henrick, Bethany M. |
Advisor: | Rosenthal, Kenneth L. Stampfli, Martin |
Department: | Medical Sciences |
Keywords: | Innate immunity; innate factors; breast milk; mother-to-child transmission; Toll-like receptor 2 (TLR2); soluble Toll-like receptor 2 (sTLR2);Medical Immunology;Virus Diseases;Medical Immunology |
Publication Date: | Oct-2013 |
Abstract: | <p>Breastfeeding from HIV-infected mothers is one of the major sources of pediatric HIV-1 infection; however, an intervention that promotes exclusive breastfeeding has significantly reduced vertical HIV transmission rates and infant mortality. The mechanisms underlying this phenomenon remain unknown; however, have been closely linked to high levels of innate immune factors in breast milk. Indeed, the level of several innate factors in breast milk correlate with protection and/or have direct anti-viral properties <em>in vitro.</em> The innate immune factor, soluble TLR2 (sTLR2) is found in high concentration in breast milk and has previously been investigated for its anti-bacterial properties; however, its anti-viral properties remain poorly understood. Thus, the research presented in this thesis extended our understanding of sTLR2 by characterizing the mechanisms by which sTLR2 inhibited HIV-induced inflammation and infection. Chapter 2 examined the predominant forms of sTLR2 in breast milk from different women, its cellular source, bioavailability and kinetics postpartum. Functionally, we confirmed sTLR2’s anti-bacterial properties and extended to show, for the first time, that sTLR2 directly inhibited HIV infection <em>in vitro.</em> Chapter 3 documented a potential mechanism of sTLR2’s direct inhibition of HIV infection <em>in vitro</em> and, investigated sTLR2 and TLR2 expression in HIV uninfected compared to HIV infected breast milk and breast milk cells, respectively. Chapter 4 investigated the role of TLR2’s recognition of novel HIV pathogen associated molecular patterns (PAMPs), and whether TLR2 expression increased HIV infection and integration. Taken together, we present novel anti-viral functions of sTLR2 by demonstrating that sTLR2 bound to specific HIV PAMPs, which led to significantly decreased HIV-induced inflammation, co-receptor expression, and HIV infection. Furthermore, we demonstrated, for the first time, that TLR2 recognizes specific HIV PAMPs, which led to significantly increased pro-inflammatory cytokine production, co-receptor expression and HIV infection. Thus, sTLR2 and TLR2 represent innate immune factors that might have preventative and therapeutic applications for both infants and adults in the future.<strong><br /> </strong></p> |
URI: | http://hdl.handle.net/11375/13312 |
Identifier: | opendissertations/8130 9233 4569550 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Size | Format | |
---|---|---|---|
fulltext.pdf | 37.48 MB | Adobe PDF | View/Open |
Items in MacSphere are protected by copyright, with all rights reserved, unless otherwise indicated.