Szylar, Gabriella Sophie;
(2020)
Effects of regulatory T cells on macrophage inflammatory responses to Streptococcus pneumoniae.
Doctoral thesis (Ph.D), UCL (University College London).
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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.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Effects of regulatory T cells on macrophage inflammatory responses to Streptococcus pneumoniae |
| Event: | UCL |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | 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. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10109393 |
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