eprintid: 10109393 rev_number: 27 eprint_status: archive userid: 608 dir: disk0/10/10/93/93 datestamp: 2020-11-05 12:29:56 lastmod: 2021-10-02 22:10:42 status_changed: 2020-11-05 12:29:56 type: thesis metadata_visibility: show creators_name: Szylar, Gabriella Sophie title: Effects of regulatory T cells on macrophage inflammatory responses to Streptococcus pneumoniae ispublished: unpub divisions: UCL divisions: B02 divisions: C10 divisions: D17 note: Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. abstract: Streptococcus pneumoniae infection remains a major cause of morbidity and mortality worldwide. An effective inflammatory response is crucial for clearance of the pathogen, but excessive inflammation causes serious complications and host damage. Macrophages are the initiators of inflammation and exhibit plasticity in their responses ranging from highly pro-inflammatory to anti-inflammatory actions. Forkhead box p3 (Foxp3)-expressing Regulatory T (Treg) cells can dampen the inflammatory effects of various cell types. Co-culture of monocyte-derived macrophages (MDM) with Treg cells prior to or during S. pneumoniae infection and measurement of tumour necrosis factor α (TNFα), interleukin (IL)-6 and IL-1β in the supernatant was used to identify anti-inflammatory effects of Treg cells on MDMs. Treg cells potently reduced MDM pro-inflammatory cytokine production when co-cultured prior to infection, in a manner requiring direct Treg-MDM cell contact. This anti-inflammatory effect did not occur upon infection with Acinetobacter baumannii, indicating a degree of pathogen-specificity. Treg cells also reduced MDM responses to S. pneumoniae when added to the MDMs during infection, but to a lesser extent than pre-infection co-culture. A human intradermal S. pneumoniae challenge model was used to examine T cell recruitment, and a potential Treg population was identified. Using normal human lung sections, Foxp3+ and Foxp3- cells were identified by immunofluorescent (IF) staining, indicating the potential presence of lung-resident Treg cells. Overall, the data demonstrate that Treg cells can reduce macrophage pro-inflammatory cytokine production to S. pneumoniae. Provisional data indicate that Treg cells may recruit in response to S. pneumoniae in a human model by 48 hours post-challenge, and Foxp3+ cell are present in normal human lung. date: 2020-09-28 date_type: published oa_status: green full_text_type: other thesis_class: doctoral_open thesis_award: Ph.D language: eng thesis_view: UCL_Thesis primo: open primo_central: open_green verified: verified_manual elements_id: 1811656 lyricists_name: Szylar, Gabriella lyricists_id: GSSZY46 actors_name: Austen, Jennifer actors_id: JAUST66 actors_role: owner full_text_status: public pages: 392 event_title: UCL institution: UCL (University College London) department: Division of Medicine thesis_type: Doctoral citation: Szylar, Gabriella Sophie; (2020) Effects of regulatory T cells on macrophage inflammatory responses to Streptococcus pneumoniae. Doctoral thesis (Ph.D), UCL (University College London). Green open access document_url: https://discovery-pp.ucl.ac.uk/id/eprint/10109393/1/Corrected%20Final%20Thesis%20Gabriella%20Szylar.pdf