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Innate immune recognition of intracellular DNA as 'stranger' and 'danger' signal

Objective

The innate immune system provides an immediate response to infection and injury. It relies on the detection of pathogen-associated molecular patterns (PAMPs), molecular hallmarks of infection which are shared amongst different pathogens but are absent from healthy host cells. The detection of intracellular DNA as PAMP has emerged a key event in the innate immune response to DNA viruses, retroviruses and intracellular bacteria. In some circumstances the body’s own DNA can also be also detected as a danger-associated molecular pattern (DAMP), e.g. when DNA from dying cells is not cleared effectively, and this can play a role in the development of autoimmune conditions such as systemic lupus erythematosus.
One of the responses to foreign DNA is the secretion of interferons and pro-inflammatory cytokines, which then help to establish an antiviral state in the infected cell and its neighbours, and alert more specialised immune cells to the danger. Several proteins have been proposed to act as interferon-inducing DNA receptors, including most recently the enzyme cyclic GMP-AMP synthase, which provides a particularly elegant signalling pathway through production of cyclic GMP-AMP as second messenger. However, it is no yet know whether other receptor proteins also utilise this signalling pathway, how signalling is regulated, and how foreign DNA is distinguished from the cell's own genome.
The objectives of this project are:
1.) To test the involvement of DNA receptors in the recognition of DNA as 'stranger' and 'danger' signal in human cells
2.) To examine the interplay between DNA receptor candidates
3.) To identify novel regulators of the DNA-induced signalling pathway
4.) To define the nature of the DNA ligand that is recognised by innate immune receptors
By elucidating the molecular mechanisms of DNA sensing by the innate immune system, this project has great scientific and medical relevance for the fields of infection, vaccination and autoimmunity.

Field of science

  • /natural sciences/biological sciences/microbiology/virology
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /medical and health sciences/basic medicine/immunology
  • /natural sciences/biological sciences/genetics and heredity/genome
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins/enzymes

Call for proposal

FP7-PEOPLE-2013-CIG
See other projects for this call

Funding Scheme

MC-CIG - Support for training and career development of researcher (CIG)

Coordinator

UNIVERSITY OF LANCASTER
Address
Bailrigg
LA1 4YW Lancaster
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 70 833,33
Administrative Contact
Toni Elsworth-Ross

Participants (1)

UNIVERSITY OF DUNDEE

Participation ended

United Kingdom
EU contribution
€ 29 166,67
Address
Nethergate
DD1 4HN Dundee
Activity type
Higher or Secondary Education Establishments
Administrative Contact
James Mcgregor (Mr.)