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The Importance of TLR2 and Macrophages in Modulating a Humoral Response after Encountering Streptococcus pneumoniae
Uniformed Services University Of The Health Sciences Bethesda United States
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Streptococcus pneumoniae Pn is an important pathogen in many community-acquired infections, including acute bacterial sinusitis, community-acquired pneumonia, as well as in more invasive infections, such as meningitis and bacteremia.Toll-like receptors TLRs are a family of 12 transmembrane proteins that recognize pathogens and are expressed on various immune cells including macrophages M,dendritic cells DC, T and B, cells and they play an important role in the initial recognition of pathogens by binding conserved moieties known as pathogen associated molecular patterns PAMPs. Pn is known to contain ligands for TLR2, TLR4, TLR78,and TLR9 that can act collectively to initiate innate immunity. This is largely mediated through phagocytosis and intracellular killing by neutrophils and macrophages that are recruited to, and activated at, the site of infection 1. Adaptive immunity is initiated when professional antigen-presenting cells APCs, such as macrophages M and dendritic cells DC recognize microbial surface components via cell surface receptorsi.e. TLRs and scavenger receptors phagocytose the bacterium, produce numerous cytokineschemokines and migrate to secondary lymphoid organs such as the spleen and lymph nodes. Once in the secondary lymphoid tissue, the APCs activate T cells leading to many immune effector mechanisms, including the production of antibodies by B cells. In the following dissertation, I have used a murine model to study the host response to Pn.
APPROVED FOR PUBLIC RELEASE