Recruitment of neutrophils to the lymph node and their role at steady state and after Staphylococcus aureus infection

dc.contributor.advisorKubes, Paul
dc.contributor.authorBogoslowski, Ania
dc.contributor.committeememberMody, Christopher
dc.contributor.committeememberOusman, Shalina
dc.contributor.committeememberFinney, Constance
dc.contributor.committeememberJohnston, William Brent
dc.date2020-06
dc.date.accessioned2020-03-30T22:16:26Z
dc.date.available2020-03-30T22:16:26Z
dc.date.issued2020-03-25
dc.description.abstractThe contribution of lymph nodes to the adaptive immune response is well studied. However, their function as an innate immune organ has been overlooked. In this thesis, neutrophils are identified in the lymph node at steady state. The entry of these neutrophils is entirely dependent upon L-selectin. After entering the lymph node, neutrophils at steady state will recirculate, exiting from the lymph node via efferent lymphatics in an S1P-dependent manner. In mice co-housed with pet store mice, there is an increased number of neutrophils in the lymph nodes at steady state. These neutrophils act as reconnaissance cells to recruit additional neutrophils after infection. We observed that after infection in the foot, there is very little dissemination past the popliteal lymph node and into the peripheral organs. In four hours, the number of neutrophils in the lymph node increases dramatically from steady state. Neutrophil entry proceeds through the high endothelial venules (HEV) and can occur via direct L-selectin-Peripheral node addressin (PNAd) interactions or through a bridging mechanism involving neutrophil P-selectin glycoprotein ligand-1 (PSGL-1) and platelet- P-selectin binding to PNAd on HEV. C5a is necessary for neutrophil recruitment, but it is independent of C-C chemokine receptor type 7 (CCR7) and lymph node resident macrophages. Blocking neutrophil recruitment using anti-PNAd antibody resulted in bacterial dissemination, demonstrating the contribution of neutrophils to the innate immune function of the lymph node. Finally, this thesis begins to assess the contribution of lymph node innervation to the above processes. Sympathetic innervation may play a greater role than sensory innervation, at least as it pertains to neutrophils, as determined by the methods used here. This work still establishes an important basis for future examination of the effect of innervation on other cell types in the lymph node. Overall, this body of work has made important contributions to the understanding of neutrophil biology in the context of the lymph node, both at steady state and after infection.en_US
dc.identifier.citationBogoslowski, A. (2020). Recruitment of neutrophils to the lymph node and their role at steady state and after Staphylococcus aureus infection (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/37652
dc.identifier.urihttp://hdl.handle.net/1880/111759
dc.language.isoengen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.en_US
dc.subjectneutrophilen_US
dc.subjectlymph nodeen_US
dc.subjectL-selectinen_US
dc.subjectStaphylococcus aureusen_US
dc.subjectsteady stateen_US
dc.subjectintravital imagingen_US
dc.subject.classificationImmunologyen_US
dc.titleRecruitment of neutrophils to the lymph node and their role at steady state and after Staphylococcus aureus infectionen_US
dc.typedoctoral thesisen_US
thesis.degree.disciplineMedicine – Immunologyen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameDoctor of Philosophy (PhD)en_US
ucalgary.item.requestcopytrueen_US
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