Objective
Sepsis, the systemic inflammatory host response to infection, is a major health problem. Inflammation is considered the first line of defence in host-pathogen interactions. Granzymes (grzs) are a family of proteases released from secretory granules that have been suggested to have relevant effects in inflammation. Outstanding findings are the rationale to hypothesize that granzymes play an essential role in the host response to bacterial sepsis: various bacteria can induce release of GrzA and B by leukocytes; elevated plasma levels of GrzA and B have been found in patients with sepsis; intravenous injection of LPS into healthy humans is a potent inducer of GrzA and B; deficient mice in GrzA and M are resistant to LPS-induced systemic inflammation and lethality; and GrzA-deficient mice show an improved host defence during pneumonia caused by S. pneumoniae.
The aim of the proposed project is to determine the role of GrzA, B and M in host response to bacterial sepsis, studying which cells produce them and via which receptors this production is induced, and what their function is during sepsis. For this purpose, we will use mouse models of sepsis, pneumonia and peritonitis (the most common causes of sepsis) and human subjects from the Intensive Care Unit with and without sepsis and healthy controls. We will determine grzs producing cell types and grzs plasma levels both in humans and mice. We will examine the role of Toll-like receptors (TLR) in the bacterial induction of grzs in splenocytes from TLR-deficient mice incubated with relevant bacteria, and then compare grzs expression of wild-type and TLR-deficient mice with sepsis. Finally, grz-deficient mice will be compared with normal wild-type mice with regard to key host responses during pneumonia, peritonitis or primary sepsis.
This project will provide in depth information on the regulation of grzs production during sepsis and their contribution to the host response during severe bacterial infection.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences clinical medicine pneumology
- natural sciences biological sciences microbiology bacteriology
- medical and health sciences clinical medicine critical care medicine
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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)
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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.
FP7-PEOPLE-2011-IEF
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Funding Scheme
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.
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
1105AZ Amsterdam
Netherlands
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.