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The human lung immune responses to nasopharyngeal pneumococcal colonisation in healthy adults

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Mitsi, Elena (2019) The human lung immune responses to nasopharyngeal pneumococcal colonisation in healthy adults, Thesis (Doctoral), Liverpool School of Tropical Medicine.

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E Mitsi - PhD Thesis.pdf - Accepted Version
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Abstract

Pneumococcal pneumonia burden remains high globally, affecting the youngest, the oldest and immunocompromised individuals worldwide. Colonisation of the human nasopharynx with S. pneumoniae is a pre-requisite for the development of pneumococcal disease and the primary reservoir for transmission. Paradoxically, it is also the main source of naturally acquired immunity. Currently, there is limited knowledge on how nasopharyngeal pneumococcal colonisation impacts on the lung immune responses in humans. Experimental human pneumococcal colonisation offers a safe way to study the dynamics between a known start-point colonisation episode and the lung immune responses.
The data presented in this thesis show that colonisation of the nasopharynx with S. pneumoniae is an immunising event for the human lung, affecting both the innate and adaptive arm of immunity. Alveolar macrophage activation and function were altered post colonisation, leading to increased opsonophagocytic capacity that persisted for up to three months post the challenge. The overall skewed CD4+ Th-1 responses observed in the lung indicate that CD4+ T cells may prime alveolar macrophage through IFN-γ secretion. In vitro stimulation of lung lymphocytes with pneumococcus suggest that TCR-γδ T cells can stand as an additional source of IFN-γ in vivo. As described before, pneumococcal colonisation seeded the human lung with cognate, IL-17 secreting, CD4+ T cells- the only observed memory population amongst lung T cells. Antibody levels against the capsule of the challenge strain were also elevated post colonisation. Pneumococcal cells found in the lung days to weeks after clearance of nasal colonisation suggest that they may be the stimulus for the observed enhanced lung immunity. Collectively, the data presented here support the use of respiratory tract as route for effective pneumococcal vaccination. On the other hand, they emphasize that heavily colonised individuals with defective alveolar macrophage function or elderly due to lack of colonisation are at increased risk to develop pneumonia.

Item Type: Thesis (Doctoral)
Subjects: QU Biochemistry > Cells and Genetics > QU 375 Cell physiology
QW Microbiology and Immunology > Immunity by Type > QW 541 Natural immunity. Immunogenetics
QW Microbiology and Immunology > Immunity by Type > QW 551 Acquired immunity. Artificial immunity
WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 217 Pneumococcal infections
WF Respiratory System > Lungs > WF 600 Lungs
WV Otolaryngology > Nose and Paranasal Sinuses > WV 300 General works
WV Otolaryngology > Pharyngeal Region > WV 400 General works
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Item titleItem URI
Interaction between the nasal microbiota and S. pneumoniae in the context of live-attenuated influenza vaccine.http://archive.lstmed.ac.uk/11189/
Inflammation induced by influenza virus impairs innate control of human pneumococcal carriagehttp://archive.lstmed.ac.uk/9017/
Agglutination by anti-capsular polysaccharide antibody is associated with protection against experimental human pneumococcal carriagehttp://archive.lstmed.ac.uk/6241/
Innate and adaptive nasal mucosal immune responses following experimental human pneumococcal colonizationhttp://archive.lstmed.ac.uk/11342/
Single use and conventional bronchoscopes for Broncho alveolar lavage (BAL) in research: a comparative study (NCT 02515591)http://archive.lstmed.ac.uk/7103/
Nasal Pneumococcal Density is Associated with Microaspiration and Heightened Human Alveolar Macrophage Responsiveness to Bacterial Pathogenshttp://archive.lstmed.ac.uk/12865/
Hands are vehicles for transmission of Streptococcus pneumoniae in novel controlled human infection studyhttp://archive.lstmed.ac.uk/9459/
Minimally Invasive Nasal Sampling in Children Offers Accurate Pneumococcal Colonization Detectionhttp://archive.lstmed.ac.uk/12775/
Human alveolar macrophages predominately express combined classical M1 and M2 surface markers in steady statehttp://archive.lstmed.ac.uk/8560/
Antibodies Reactive to Commensal Streptococcus mitis Show Cross-Reactivity With Virulent Streptococcus pneumoniae Serotypeshttp://archive.lstmed.ac.uk/8601/
Pneumococcal colonization in healthy adult research participants in the conjugate vaccine era, United Kingdom, 2010—2017http://archive.lstmed.ac.uk/10018/
Protective effect of PCV vaccine against experimental pneumococcal challenge in adults is primarily mediated by controlling colonisation densityhttp://archive.lstmed.ac.uk/11026/
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Depositing User: Lynn Roberts-Maloney
Date Deposited: 28 May 2020 10:21
Last Modified: 28 May 2020 10:21
URI: https://archive.lstmed.ac.uk/id/eprint/14526

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