Objective
To evaluate the role of T cell-associated lytic mechanisms in the killing of intracellular mycobacteria, and the contribution of these effector pathways to immunity against tuberculosis and leprosy.
Expected Outcome
The study will obtain scientific data allowing the relative importance of these immune responses in protection against mycobacterial disease, and the heterogeneity of the P2Z (P2X7) receptor in susceptibility to mycobacterial disease, to be evaluated.
The function of various T cell subsets in immunity to tuberculosis will be assessed in patients with tuberculosis, without or with co-infection with HIV, and in normal BCG-vaccinated healthy controls. Further studies will assess expression of the P2Z (P2X7) receptor in patients with tuberculosis or leprosy, and in healthy controls. Specific areas of investigation are as follows:
* To evaluate whether antigen-specific CD4+ and CD8+ T-cell mediated cytotoxicity reduces the survival of intracellular maycobacteria within macrophages, and the relative contribution of various cytolytic effector mechanisms to this T cell-induced macrophage death (LSHTM, London , University of Oxford, and MRC Laboratories, The Gambia)
* To assess the role of the gd T cell subset in cytolysis and cytokine secretion in tuberculosis with/without HIV co-infection (CMDT, Lisbon)
* To investigate the mechanism(s) by which extracellular ATP-induced macrophage death (occurring via the P2Z-receptor mediated pathway) reduces survival of intracellular M. bovis BCG, and to extend these studies to other pathogenic mycobacteria (University of Birmingham)
* To investigate the role of genetic heterogeneity of extracellular ATP-induced macrophage death and intracellular mycobacterial killing in conferring resistance to mycobacterial disease, by comparing P2Z (P2X7) receptor expression on monocyte-derived macrophages from patients with tuberculosis (with/without HIV), lepromatous leprosy, and endemic controls (University of Birmingham, CMDT Lisbon, MRC Laboratories, The Gambia and IMSS Mexico City).
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine immunology
- medical and health sciences health sciences infectious diseases RNA viruses HIV
- medical and health sciences clinical medicine pneumology tuberculosis
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
WC1E 7HT London
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.