MCCIR AZ GSK Update Seminar Series
| Dates: | 11 January 2016 |
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| Times: | 15:30 - 16:30 |
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| What is it: | Seminar |
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| Organiser: | Faculty of Life Sciences |
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| Who is it for: | University staff, Current University students |
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The next MCCIR AZ/GSK Update Seminar is taking place on Monday the 11th of January 2016
Understanding macrophage regulatory pathways in infant vulnerability to tuberculosis
Anu Goenka
In infants, tuberculosis (TB) carries a major morbidity and mortality in significant part because of miliary disease and meningitis. The mechanisms underlying infant vulnerability to disseminated TB are poorly understood. In particular, the ability of innate cells to contain and kill Mycobacterium tuberculosis has not previously been compared between infants and adults. This project aims to explore the overarching hypothesis that antimycobacterial immunity in infants is impaired because of a relatively untrained innate immune response. Candidate mechanisms include ineffective phagocytosis, containment and bacillary killing in infant macrophages, monocytes and neutrophils. Preliminary work has explored the use of techniques to assess antimycobacterial functional outcomes in infant and adult blood. Key initial findings include: i) A significantly lower mycobacterial load in IFN?-treated monocyte-derived macrophages as assessed by high-throughput imaging cytometry; ii) Elevated IFN? in infant whole blood stimulated with Bacille Calmette-Guérin compared with adult equivalents, which may contribute to an impaired response to protective IFN? in the infant; iii) Poor reproducibility of assays involving monocyte-derived macrophages (MDMs) owing to differences in cell adherence and survival between donors. Based on this work, we are now assessing responses in freshly isolated infant monocytes and neutrophils, and their adult equivalents, in the presence and absence of polarising signals such as IFN?. The internalisation and endosomal persistence of GFP-tagged bacilli is being evaluated by high-throughput imaging cytometry. Mycobacterial killing is being assessed by measuring bioluminescence of neutrophils infected with luciferase-tagged mycobacteria. Understanding the mechanisms underlying the functional differences observed in the work outlined above will provide novel strategies to modulate infant innate immune ontogeny. Such therapies may not only provide a conduit to improve antimycobacterial immunity, but also responses to heterologous stimuli such as allergens and vaccines.
Lung macrophage regulation during development
Samira Salek-ardakani
Abstract TBC
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Michael Smith Lecture Theatre
Michael Smith Building
Manchester
