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Title: Characterization of pulmonary langerin-expressing dendritic cells in a model of respiratory viral infection
Author: Poux, Candice Maria Yvette
ISNI:       0000 0004 2726 3222
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2011
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Understanding the control of pulmonary dendritic cells (DC) function during respiratory virus infection may lead to novel prophylactic and antiviral therapeutic strategies, Three subsets have already been identified: plasmacytoid DC (pDCL eerie DC and CD103+ DC which express the C-type lectin langerin. To further characterize the different pulmonary DC, experiments were undertaken in transgenic eGFP/DTR F1 mice, in which all langerin-expressing cells express eGFP and human diphtheria toxin receptor (DTRL) offering the unique possibility to address the role of CD103+ DC, , both during homeostatic and inflammation states. Interestingly, immunophenotyping of pulmonary DC from these mice demonstrated that not all CD103+ DC are tang", but both subsets exhibited an immature phenotype in the lung and mature upon arrival in the mediastinal lymph node (mLNL) suggesting the possibility of immune redundancy. Sendai virus (SeVL) a mouse parainfluenza virus, causes acute viral inflammation of the small airways that is comparable to viral bronchiolitis in humans, We generated a recombinant SeV that expresses a red fluorescent protein/ovalbumin fusion protein (SeV-OVATdT), It was designed to help tracking viral infection in vivo and to perform functional studies addressing the role of pulmonary DC during respiratory virus infection. At 5 days post-infection, SeV-OVATdT induced bronchiolitis and interstitial pneumonia equivalent to SeV WT infection, and significant changes in pulmonary DC populations compared to mock-infected controls. Specifically, all DC characterized here increased in SUMMARY 1 - PAGE 2 significantly more inflammatory DC and CD8a+ DC were found in mLN, while number of pulmonary pDC was maintained. Additionally, viral replication was restrained and significantly more SeV- specific CD8+ T cells were recruited to lungs. Altogether, these results indicate that pulmonary CD103+ l.ang" DC negatively modulate antiviral immune responses.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available