Innate immune governance of the fate of inflammatory monocytes in tuberculosis. (360G-Wellcome-104453_Z_14_Z)
Circulating monocytes contribute to tissue resident macrophages at inflammatory foci. Existing data suggest that differential innate immune host-pathogen interactions govern the fate of monocytes and functional heterogeneity of macrophages to influence the outcome of disease in models of Mycobacterium leprae and Mycobacterium marinum infection. I aim to address the question that innate immune interactions also influence the fate and function of monocytes recruited to foci of Mycobacterium tuberc ulosis (Mtb) infection, and inform our understanding of alternative outcomes of tuberculosis (TB) in which macrophages play an important role. In this fellowship, I will test the hypothesis that inflammatory monocytes associated with virulent Mtb strains differentiate to macrophages that support greater mycobacterial growth than those associated with avirulent strains. I will specifically investigate the role of Toll-like receptor 2 dependent innate immune responses to Mtb on the fate inflammato ry monocytes and extend these experimental models to identify the molecular mechanisms which support monocyte survival and influence intracellular mycobacterial restriction. In parallel, I will assess the physiological significance of my in vitro model by testing the hypothesis that transcriptional signatures of monocytes differentiated in vitro by Mtb stimulated innate immune responses are reflected in macrophages at the site disease in human TB.
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Grant Details
Amount Awarded | 234234 |
Applicant Surname | Mehta |
Approval Committee | Clinical Interview Committee |
Award Date | 2014-06-25T00:00:00+00:00 |
Financial Year | 2013/14 |
Grant Programme: Title | Research Training Fellowship |
Internal ID | 104453/Z/14/Z |
Lead Applicant | Dr Meera Mehta |
Partnership Value | 234234 |
Planned Dates: End Date | 2018-11-30T00:00:00+00:00 |
Planned Dates: Start Date | 2014-09-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Greater London |
Sponsor(s) | Prof Judith Breuer |