{"id":{"repo_id":"queens","oai_identifier":"oai:queensu.scholaris.ca:1974/24492"},"canonical_url":"https://search.dev.ndltd.org/etd/queens/oai:queensu.scholaris.ca:1974/24492","repository":{"repo_id":"queens","name":"Queens University","base_url":"https://qspace.library.queensu.ca/server/oai/request"},"display":{"title":"Novel cytokines in innate immunity: IL-27 and IL-30 enhance responsiveness to gram-negative bacterial components in human myeloid cells","abstract":"In response to microbial stimuli, innate myeloid cells are potent producers of cytokines that function to mediate inflammation. This thesis investigates two related cytokines, IL-27 and IL-30, to identify novel proinflammatory mechanisms to improve treatments for bacterial infections. IL-27 is comprised of IL-27p28 and EBI3 subunits; the IL-27p28 subunit, also named IL-30, can also signal independently of EBI3. To date, most studies on IL-27 have focused on its role in CD4+ T cell differentiation. IL-30 has been recognized as an antagonist of IL-6, IL-11, and IL-27 in CD4+ T cells. In primary monocytes, IL-27 promotes proinflammatory cytokine production and TLR4 expression in monocytes for a potent inflammatory response to bacterial endotoxin, LPS. Barring these studies, functions of IL-27 and IL-30 in human myeloid cells have not been well described, and therefore are the focus of this thesis. Specifically, this thesis compares IL-27 and IL-30 signaling in human monocytes and explores novel proinflammatory effects of IL-27 and IL-30 on cytokine production in response to either Gram-negative bacteria or bacterial components in myeloid cells. The effects of IL-27 are explored in Salmonella enterica infection, NLRP3 inflammasome activation, and induction of endotoxin (LPS) tolerance in human monocytes and macrophages, while the effects of IL-30 are defined in human monocytes. IL-27 and IL-30 induce IP-10 production in human monocytes in a STAT-dependent manner. Furthermore, pre-treatment with IL-6 interferes with IL-27 and IL-30 functions in human monocytes. Similarly to TLR4, IL-27 treatment also enhances TLR5 expression in human monocytes and macrophages, inducing cytokine production in response to TLR agonists LPS and flagellin or S. enterica infection. IL-27 also increases LPS/ATP-mediated NLRP3 inflammasome activation and IL-1β production in human monocytes via upregulated TLR4 and P2X7 expression. Comparing human THP-1 monocytes and PMA-differentiated THP-1 macrophages, CD14 expression plays a role in LPS and IL-27 responsiveness, whereby IL-27-mediated inhibition of LPS tolerance is greater in CD14low THP-1 monocytes compared to CD14high PMA-differentiated THP-1 macrophages. Overall, this thesis demonstrates novel proinflammatory roles for IL-27 and its subunit IL-30 in innate immune responses and may serve as novel adjuvant candidates for vaccine design against Gram-negative bacterial infections.","abstract_html":"In response to microbial stimuli, innate myeloid cells are potent producers of cytokines that function to mediate inflammation. This thesis investigates two related cytokines, IL-27 and IL-30, to identify novel proinflammatory mechanisms to improve treatments for bacterial infections. IL-27 is comprised of IL-27p28 and EBI3 subunits; the IL-27p28 subunit, also named IL-30, can also signal independently of EBI3. To date, most studies on IL-27 have focused on its role in CD4+ T cell differentiation. IL-30 has been recognized as an antagonist of IL-6, IL-11, and IL-27 in CD4+ T cells. In primary monocytes, IL-27 promotes proinflammatory cytokine production and TLR4 expression in monocytes for a potent inflammatory response to bacterial endotoxin, LPS. Barring these studies, functions of IL-27 and IL-30 in human myeloid cells have not been well described, and therefore are the focus of this thesis. Specifically, this thesis compares IL-27 and IL-30 signaling in human monocytes and explores novel proinflammatory effects of IL-27 and IL-30 on cytokine production in response to either Gram-negative bacteria or bacterial components in myeloid cells. The effects of IL-27 are explored in Salmonella enterica infection, NLRP3 inflammasome activation, and induction of endotoxin (LPS) tolerance in human monocytes and macrophages, while the effects of IL-30 are defined in human monocytes. IL-27 and IL-30 induce IP-10 production in human monocytes in a STAT-dependent manner. Furthermore, pre-treatment with IL-6 interferes with IL-27 and IL-30 functions in human monocytes. Similarly to TLR4, IL-27 treatment also enhances TLR5 expression in human monocytes and macrophages, inducing cytokine production in response to TLR agonists LPS and flagellin or S. enterica infection. IL-27 also increases LPS/ATP-mediated NLRP3 inflammasome activation and IL-1β production in human monocytes via upregulated TLR4 and P2X7 expression. Comparing human THP-1 monocytes and PMA-differentiated THP-1 macrophages, CD14 expression plays a role in LPS and IL-27 responsiveness, whereby IL-27-mediated inhibition of LPS tolerance is greater in CD14low THP-1 monocytes compared to CD14high PMA-differentiated THP-1 macrophages. Overall, this thesis demonstrates novel proinflammatory roles for IL-27 and its subunit IL-30 in innate immune responses and may serve as novel adjuvant candidates for vaccine design against Gram-negative bacterial infections.","abstract_has_math":false,"creators":["Petes, Carly"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":"Biomedical and Molecular Sciences","school":null,"contributors":[],"advisors":["Gee, Katrina"],"committee_chairs":[],"committee_members":[],"year":null,"date_issued":"","date_published":null,"updated_at":"2026-07-27T20:35:31Z","subjects":["Interleukin-27","Lipopolysaccharide","Innate immunity","Myeloid cells","Gram-negative bacteria","Interleukin-30"],"languages":["eng"],"rights":["Attribution-NonCommercial-NoDerivs 3.0 United States"],"rights_urls":["http://creativecommons.org/licenses/by-nc-nd/3.0/us/"],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1974/24492","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.department","label":"Department","values":["Biomedical and Molecular Sciences"]},{"key":"dc:contributor.supervisor","label":"Supervisor","values":["Gee, Katrina"]},{"key":"dc:creator","label":"Author","values":["Petes, Carly"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2018-09-04T23:30:00Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2018-09-04T23:30:00Z"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Interleukin-27","Lipopolysaccharide","Innate immunity","Myeloid cells","Gram-negative bacteria","Interleukin-30"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Attribution-NonCommercial-NoDerivs 3.0 United States"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://creativecommons.org/licenses/by-nc-nd/3.0/us/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1974/24492"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["In response to microbial stimuli, innate myeloid cells are potent producers of cytokines that function to mediate inflammation. This thesis investigates two related cytokines, IL-27 and IL-30, to identify novel proinflammatory mechanisms to improve treatments for bacterial infections. IL-27 is comprised of IL-27p28 and EBI3 subunits; the IL-27p28 subunit, also named IL-30, can also signal independently of EBI3. To date, most studies on IL-27 have focused on its role in CD4+ T cell differentiation. IL-30 has been recognized as an antagonist of IL-6, IL-11, and IL-27 in CD4+ T cells. In primary monocytes, IL-27 promotes proinflammatory cytokine production and TLR4 expression in monocytes for a potent inflammatory response to bacterial endotoxin, LPS. Barring these studies, functions of IL-27 and IL-30 in human myeloid cells have not been well described, and therefore are the focus of this thesis. Specifically, this thesis compares IL-27 and IL-30 signaling in human monocytes and explores novel proinflammatory effects of IL-27 and IL-30 on cytokine production in response to either Gram-negative bacteria or bacterial components in myeloid cells. The effects of IL-27 are explored in Salmonella enterica infection, NLRP3 inflammasome activation, and induction of endotoxin (LPS) tolerance in human monocytes and macrophages, while the effects of IL-30 are defined in human monocytes. IL-27 and IL-30 induce IP-10 production in human monocytes in a STAT-dependent manner. Furthermore, pre-treatment with IL-6 interferes with IL-27 and IL-30 functions in human monocytes. Similarly to TLR4, IL-27 treatment also enhances TLR5 expression in human monocytes and macrophages, inducing cytokine production in response to TLR agonists LPS and flagellin or S. enterica infection. IL-27 also increases LPS/ATP-mediated NLRP3 inflammasome activation and IL-1β production in human monocytes via upregulated TLR4 and P2X7 expression. Comparing human THP-1 monocytes and PMA-differentiated THP-1 macrophages, CD14 expression plays a role in LPS and IL-27 responsiveness, whereby IL-27-mediated inhibition of LPS tolerance is greater in CD14low THP-1 monocytes compared to CD14high PMA-differentiated THP-1 macrophages. Overall, this thesis demonstrates novel proinflammatory roles for IL-27 and its subunit IL-30 in innate immune responses and may serve as novel adjuvant candidates for vaccine design against Gram-negative bacterial infections."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["PhD"]},{"key":"dc:title","label":"Title","values":["Novel cytokines in innate immunity: IL-27 and IL-30 enhance responsiveness to gram-negative bacterial components in human myeloid cells"]}]}],"canonical_facts":{"dc:contributor.department":["Biomedical and Molecular Sciences"],"dc:contributor.supervisor":["Gee, Katrina"],"dc:creator":["Petes, Carly"],"dc:date.accessioned":["2018-09-04T23:30:00Z"],"dc:date.available":["2018-09-04T23:30:00Z"],"dc:description.abstract":["In response to microbial stimuli, innate myeloid cells are potent producers of cytokines that function to mediate inflammation. This thesis investigates two related cytokines, IL-27 and IL-30, to identify novel proinflammatory mechanisms to improve treatments for bacterial infections. IL-27 is comprised of IL-27p28 and EBI3 subunits; the IL-27p28 subunit, also named IL-30, can also signal independently of EBI3. To date, most studies on IL-27 have focused on its role in CD4+ T cell differentiation. IL-30 has been recognized as an antagonist of IL-6, IL-11, and IL-27 in CD4+ T cells. In primary monocytes, IL-27 promotes proinflammatory cytokine production and TLR4 expression in monocytes for a potent inflammatory response to bacterial endotoxin, LPS. Barring these studies, functions of IL-27 and IL-30 in human myeloid cells have not been well described, and therefore are the focus of this thesis. Specifically, this thesis compares IL-27 and IL-30 signaling in human monocytes and explores novel proinflammatory effects of IL-27 and IL-30 on cytokine production in response to either Gram-negative bacteria or bacterial components in myeloid cells. The effects of IL-27 are explored in Salmonella enterica infection, NLRP3 inflammasome activation, and induction of endotoxin (LPS) tolerance in human monocytes and macrophages, while the effects of IL-30 are defined in human monocytes. IL-27 and IL-30 induce IP-10 production in human monocytes in a STAT-dependent manner. Furthermore, pre-treatment with IL-6 interferes with IL-27 and IL-30 functions in human monocytes. Similarly to TLR4, IL-27 treatment also enhances TLR5 expression in human monocytes and macrophages, inducing cytokine production in response to TLR agonists LPS and flagellin or S. enterica infection. IL-27 also increases LPS/ATP-mediated NLRP3 inflammasome activation and IL-1β production in human monocytes via upregulated TLR4 and P2X7 expression. Comparing human THP-1 monocytes and PMA-differentiated THP-1 macrophages, CD14 expression plays a role in LPS and IL-27 responsiveness, whereby IL-27-mediated inhibition of LPS tolerance is greater in CD14low THP-1 monocytes compared to CD14high PMA-differentiated THP-1 macrophages. Overall, this thesis demonstrates novel proinflammatory roles for IL-27 and its subunit IL-30 in innate immune responses and may serve as novel adjuvant candidates for vaccine design against Gram-negative bacterial infections."],"dc:description.degree":["PhD"],"dc:identifier.uri":["http://hdl.handle.net/1974/24492"],"dc:language.iso":["eng"],"dc:rights":["Attribution-NonCommercial-NoDerivs 3.0 United States"],"dc:rights.uri":["http://creativecommons.org/licenses/by-nc-nd/3.0/us/"],"dc:subject":["Interleukin-27","Lipopolysaccharide","Innate immunity","Myeloid cells","Gram-negative bacteria","Interleukin-30"],"dc:title":["Novel cytokines in innate immunity: IL-27 and IL-30 enhance responsiveness to gram-negative bacterial components in human myeloid cells"],"dc:type":["thesis"]},"updated_at":"2026-07-27T20:35:31Z"}