The protective role of neutrophils in human tuberculosis. (360G-Wellcome-087754_Z_08_Z)

£326,500

There is mounting evidence that neutrophils are powerfully mycobactericidal and may contribute significantly to the early containment of tuberculosis infection. It is also believed that HIV compromises neutrophil number and function, which may in part explain the increased susceptibility of HIV positive people to tuberculosis. This study aims to first assess the relative contribution of neutrophils to mycobacterial restriction compared to other cell types in a whole blood model, before furthe r exploration of the mechanisms of killing. Subsequently the impact of HIV on neutrophil defense against mycobacteria will be investigated, including whether any impairment can be overcome with neutrophil enrichment. The impact of antiretroviral therapy on neutrophil number and function will be explored prospectively, aiming to assess to what extent this explains the improvements in mycobacterial suppression previously seen with this therapy. Simultaneously, in large cohorts of HIV positive people the predictive value of peripheral neutrophil count on risk of acquiring new or active tuberculosis will be evaluated. The ultimate therapeutic aim would be to consider enhancing neutrophil count or function in recently exposed tuberculosis contacts without existing evidence of infection in order to prevent them from developing disease.

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Grant Details

Amount Awarded 326500
Applicant Surname Lowe
Approval Committee International Interview Committee
Award Date 2009-03-25T00:00:00+00:00
Financial Year 2008/09
Grant Programme: Title Research Training Fellowship
Internal ID 087754/Z/08/Z
Lead Applicant Dr David Lowe
Partnership Value 326500
Planned Dates: End Date 2013-03-31T00:00:00+00:00
Planned Dates: Start Date 2009-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
Sponsor(s) Prof Geoffrey Pasvol, Prof Robert Wilkinson