Dissertation/Thesis Abstract

Macrophage receptor-mediated recognition, response and treatment of Leishmania major infection
by Nelson, Keith G., Ph.D., Colorado State University, 2011, 149; 3489901
Abstract (Summary)

We investigate the role of macrophage receptors in the recognition of Leishmania major and response to the parasite, focusing on complement receptors (CR). CR1 and CR3 are the main complement receptors on murine macrophages, recognizing specific parasite surface antigens and parasites opsonized by complement component 3 (C3). Utilizing C3-deficient mice, we show a clear role for complement in enhancing parasite infectivity, and recognition of and response to L. major by the murine host. In our in vitro experiments blocking CR1 and CR3, there is a clear effect of the route of parasite recognition and entry into the macrophage on parasite phagocytosis and cytokine response to infection by L. major, although Th1/Th2 bias is unaffected by blocking complement receptors. Using parasite strains lacking in the two most common surface molecules of L. major (LPG and gp63), we show a strong role for gp63 in the interaction with C3 and complement receptors, particularly CR3. Lastly, we demonstrate the utility of targeting anti–leishmanial therapeutics in infected hosts to the macrophage through another macrophage receptor, the scavenger receptor.

Indexing (document details)
Advisor: Mason, Gary
Commitee: Bamburg, James, Gentry-Weeks, Claudia, Zeidner, Nordin
School: Colorado State University
Department: Microbiology, Immunology, & Pathology
School Location: United States -- Colorado
Source: DAI-B 73/04, Dissertation Abstracts International
Subjects: Molecular biology, Microbiology, Parasitology
Keywords: Complement receptors, Leishmania, Macrophage receptors, Nanodisk
Publication Number: 3489901
ISBN: 9781267097453
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