{"id":{"repo_id":"vt","oai_identifier":"oai:vtechworks.lib.vt.edu:10919/73012"},"canonical_url":"https://search.dev.ndltd.org/etd/vt/oai:vtechworks.lib.vt.edu:10919/73012","repository":{"repo_id":"vt","name":"Virginia Tech","base_url":"https://vtechworks.lib.vt.edu/oai/request"},"display":{"title":"Monocyte Derived Dendritic Cells: Sentinels and Translators of Immune Response to Staphylococcus aureus","abstract":"<i>Staphylococcus aureus</i> is a versatile opportunistic pathogen causing a wide spectrum of diseases in both humans and animals. My research focused on characterization of the immune responses of monocyte derived dendritic cells (DC) to <i>S. aureus</i>. We initially evaluated the potential of circulating monocytes to serve as precursors for DC during <i>S. aureus</i> infection. The CD14⁺ monocytes, when stimulated with irradiated (ISA) or live <i>S. aureus</i> (LSA), differentiated into CD11c<sup>high</sup> CD11b<sup>high</sup> DC (MonoDC) in an autocrine fashion. This was associated with the up- regulation of granulocyte-macrophage colony stimulating factor (GMCSF) and tumor necrosis factor-α (TNF-α) gene transcription. We continued our studies to identify the role of TNF-α in the LSA induced differentiation of monocyte to MonoDC. Blocking TNF-α reduced the expression of CD11c and increased the expression of CD14 on LSA stimulated monocyte derived MonoDC. Stimulated monocytes were able to secrete monocyte chemotactic protein-1 (MCP-1), a chemokine that recruits monocytes to the site of infection/injury and induces the expression of β₂ integrins on DC. Characterization of the response of DC derived from monocytes using GMCSF and IL-4 revealed that, intact <i>S. aureus</i> rather than its purified structural components were efficient in DC activation. In response to ISA or LSA stimulation, DC induced proliferation of T cells collected from the peripheral circulation of cows with a history of <i>S. aureus</i> mastitis. Subsequent characterization of the proliferating T cells identified the presence of memory T cells. Finally, we identified a unique population of DEC205⁺CD8<sup>a+</sup> in monocyte derived DC. We further elucidated the role of DC DEC205, a C-type lectin, in <i>S. aureus</i> uptake. Blocking of receptor mediated endocytosis resulted in reduced uptake of <i>S. aureus</i> by DC. Confocal microscopy confirmed a role for DEC205 in <i>S. aureus</i> internalization and delivery to endosomes. DEC205 DC upon stimulation with <i>S. aureus</i> displayed enhanced maturation and antigen presentation. In conclusion, monocyte derived DC can uptake <i>S. aureus</i> and elicit cell mediated immune responses.","abstract_html":"&lt;i&gt;Staphylococcus aureus&lt;/i&gt; is a versatile opportunistic pathogen causing a wide spectrum of diseases in both humans and animals. My research focused on characterization of the immune responses of monocyte derived dendritic cells (DC) to &lt;i&gt;S. aureus&lt;/i&gt;. We initially evaluated the potential of circulating monocytes to serve as precursors for DC during &lt;i&gt;S. aureus&lt;/i&gt; infection. The CD14⁺ monocytes, when stimulated with irradiated (ISA) or live &lt;i&gt;S. aureus&lt;/i&gt; (LSA), differentiated into CD11c&lt;sup&gt;high&lt;/sup&gt; CD11b&lt;sup&gt;high&lt;/sup&gt; DC (MonoDC) in an autocrine fashion. This was associated with the up- regulation of granulocyte-macrophage colony stimulating factor (GMCSF) and tumor necrosis factor-α (TNF-α) gene transcription. We continued our studies to identify the role of TNF-α in the LSA induced differentiation of monocyte to MonoDC. Blocking TNF-α reduced the expression of CD11c and increased the expression of CD14 on LSA stimulated monocyte derived MonoDC. Stimulated monocytes were able to secrete monocyte chemotactic protein-1 (MCP-1), a chemokine that recruits monocytes to the site of infection/injury and induces the expression of β₂ integrins on DC. Characterization of the response of DC derived from monocytes using GMCSF and IL-4 revealed that, intact &lt;i&gt;S. aureus&lt;/i&gt; rather than its purified structural components were efficient in DC activation. In response to ISA or LSA stimulation, DC induced proliferation of T cells collected from the peripheral circulation of cows with a history of &lt;i&gt;S. aureus&lt;/i&gt; mastitis. Subsequent characterization of the proliferating T cells identified the presence of memory T cells. Finally, we identified a unique population of DEC205⁺CD8&lt;sup&gt;a+&lt;/sup&gt; in monocyte derived DC. We further elucidated the role of DC DEC205, a C-type lectin, in &lt;i&gt;S. aureus&lt;/i&gt; uptake. Blocking of receptor mediated endocytosis resulted in reduced uptake of &lt;i&gt;S. aureus&lt;/i&gt; by DC. Confocal microscopy confirmed a role for DEC205 in &lt;i&gt;S. aureus&lt;/i&gt; internalization and delivery to endosomes. DEC205 DC upon stimulation with &lt;i&gt;S. aureus&lt;/i&gt; displayed enhanced maturation and antigen presentation. In conclusion, monocyte derived DC can uptake &lt;i&gt;S. aureus&lt;/i&gt; and elicit cell mediated immune responses.","abstract_has_math":false,"creators":["Bharathan, Mini"],"institution":"Virginia Tech","degree_name":"Ph. D.","degree_level":"doctoral","degree_discipline":"Dairy Science","degree_department":"Dairy Science","school":null,"contributors":[],"advisors":[],"committee_chairs":["Mullarky, Isis K."],"committee_members":["Akers, Robert Michael","Dalloul, Rami A.","Sriranganathan, Nammalwar"],"year":2010,"date_issued":"2010-10-05","date_published":"2010-10-05","updated_at":"2026-07-22T22:19:44Z","subjects":["Staphylococcus aureus","T cells","dendritic cells","monocytes"],"languages":["en_US"],"rights":["In Copyright"],"rights_urls":["http://rightsstatements.org/vocab/InC/1.0/"],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["etd-10262010-115113"],"render_values":[{"text":"etd-10262010-115113","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/10919/73012","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.committeechair","label":"Committee Chair","values":["Mullarky, Isis K."]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Akers, Robert Michael","Dalloul, Rami A.","Sriranganathan, Nammalwar"]},{"key":"dc:contributor.department","label":"Department","values":["Dairy Science"]},{"key":"dc:creator","label":"Author","values":["Bharathan, Mini"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2016-09-22T15:14:49Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2016-09-22T15:14:49Z","2015-04-22"]},{"key":"dc:date.issued","label":"Date","values":["2010-10-05"]},{"key":"dc:publisher","label":"Institution","values":["Virginia Tech"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]},{"key":"dc:type.dcmitype","label":"Dc Type Dcmitype","values":["Text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Dairy Science"]},{"key":"thesis:degree_level","label":"Degree Level","values":["doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph. 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My research focused on characterization of the immune responses of monocyte derived dendritic cells (DC) to <i>S. aureus</i>. We initially evaluated the potential of circulating monocytes to serve as precursors for DC during <i>S. aureus</i> infection. The CD14⁺ monocytes, when stimulated with irradiated (ISA) or live <i>S. aureus</i> (LSA), differentiated into CD11c<sup>high</sup> CD11b<sup>high</sup> DC (MonoDC) in an autocrine fashion. This was associated with the up- regulation of granulocyte-macrophage colony stimulating factor (GMCSF) and tumor necrosis factor-α (TNF-α) gene transcription. We continued our studies to identify the role of TNF-α in the LSA induced differentiation of monocyte to MonoDC. Blocking TNF-α reduced the expression of CD11c and increased the expression of CD14 on LSA stimulated monocyte derived MonoDC. Stimulated monocytes were able to secrete monocyte chemotactic protein-1 (MCP-1), a chemokine that recruits monocytes to the site of infection/injury and induces the expression of β₂ integrins on DC. Characterization of the response of DC derived from monocytes using GMCSF and IL-4 revealed that, intact <i>S. aureus</i> rather than its purified structural components were efficient in DC activation. In response to ISA or LSA stimulation, DC induced proliferation of T cells collected from the peripheral circulation of cows with a history of <i>S. aureus</i> mastitis. Subsequent characterization of the proliferating T cells identified the presence of memory T cells. Finally, we identified a unique population of DEC205⁺CD8<sup>a+</sup> in monocyte derived DC. We further elucidated the role of DC DEC205, a C-type lectin, in <i>S. aureus</i> uptake. Blocking of receptor mediated endocytosis resulted in reduced uptake of <i>S. aureus</i> by DC. Confocal microscopy confirmed a role for DEC205 in <i>S. aureus</i> internalization and delivery to endosomes. DEC205 DC upon stimulation with <i>S. aureus</i> displayed enhanced maturation and antigen presentation. In conclusion, monocyte derived DC can uptake <i>S. aureus</i> and elicit cell mediated immune responses."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph. D."]},{"key":"dc:title","label":"Title","values":["Monocyte Derived Dendritic Cells: Sentinels and Translators of Immune Response to Staphylococcus aureus"]}]}],"canonical_facts":{"dc:contributor.committeechair":["Mullarky, Isis K."],"dc:contributor.committeemember":["Akers, Robert Michael","Dalloul, Rami A.","Sriranganathan, Nammalwar"],"dc:contributor.department":["Dairy Science"],"dc:creator":["Bharathan, Mini"],"dc:date.accessioned":["2016-09-22T15:14:49Z"],"dc:date.available":["2016-09-22T15:14:49Z","2015-04-22"],"dc:date.issued":["2010-10-05"],"dc:description.abstract":["<i>Staphylococcus aureus</i> is a versatile opportunistic pathogen causing a wide spectrum of diseases in both humans and animals. My research focused on characterization of the immune responses of monocyte derived dendritic cells (DC) to <i>S. aureus</i>. We initially evaluated the potential of circulating monocytes to serve as precursors for DC during <i>S. aureus</i> infection. The CD14⁺ monocytes, when stimulated with irradiated (ISA) or live <i>S. aureus</i> (LSA), differentiated into CD11c<sup>high</sup> CD11b<sup>high</sup> DC (MonoDC) in an autocrine fashion. This was associated with the up- regulation of granulocyte-macrophage colony stimulating factor (GMCSF) and tumor necrosis factor-α (TNF-α) gene transcription. We continued our studies to identify the role of TNF-α in the LSA induced differentiation of monocyte to MonoDC. Blocking TNF-α reduced the expression of CD11c and increased the expression of CD14 on LSA stimulated monocyte derived MonoDC. Stimulated monocytes were able to secrete monocyte chemotactic protein-1 (MCP-1), a chemokine that recruits monocytes to the site of infection/injury and induces the expression of β₂ integrins on DC. Characterization of the response of DC derived from monocytes using GMCSF and IL-4 revealed that, intact <i>S. aureus</i> rather than its purified structural components were efficient in DC activation. In response to ISA or LSA stimulation, DC induced proliferation of T cells collected from the peripheral circulation of cows with a history of <i>S. aureus</i> mastitis. Subsequent characterization of the proliferating T cells identified the presence of memory T cells. Finally, we identified a unique population of DEC205⁺CD8<sup>a+</sup> in monocyte derived DC. We further elucidated the role of DC DEC205, a C-type lectin, in <i>S. aureus</i> uptake. Blocking of receptor mediated endocytosis resulted in reduced uptake of <i>S. aureus</i> by DC. Confocal microscopy confirmed a role for DEC205 in <i>S. aureus</i> internalization and delivery to endosomes. DEC205 DC upon stimulation with <i>S. aureus</i> displayed enhanced maturation and antigen presentation. In conclusion, monocyte derived DC can uptake <i>S. aureus</i> and elicit cell mediated immune responses."],"dc:description.degree":["Ph. D."],"dc:identifier.other":["etd-10262010-115113"],"dc:identifier.uri":["http://hdl.handle.net/10919/73012"],"dc:language.iso":["en_US"],"dc:publisher":["Virginia Tech"],"dc:rights":["In Copyright"],"dc:rights.uri":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:subject":["Staphylococcus aureus","T cells","dendritic cells","monocytes"],"dc:title":["Monocyte Derived Dendritic Cells: Sentinels and Translators of Immune Response to Staphylococcus aureus"],"dc:type":["Dissertation"],"dc:type.dcmitype":["Text"],"thesis:degree_discipline":["Dairy Science"],"thesis:degree_level":["doctoral"],"thesis:degree_name":["Ph. D."],"thesis:institution_name":["Virginia Polytechnic Institute and State University"]},"updated_at":"2026-07-22T22:19:44Z"}