Project description
Decoding the immune evasion strategy
Group B Streptococcus (GBS) causes life-threatening infections such as sepsis and meningitis in newborns. Unfortunately, little is known about how GBS evades the human immune system. Supported by the Marie Skłodowska-Curie Actions programme, the Don’t Eat Me project will explore the use of a natural immune signal by GBS to avoid destruction by macrophages. Based on a screening of 1 500 human cellular receptors, researchers identified the inhibitory receptor SIRPα as a key interaction partner for GBS. The project’s goal is to define how GBS interacts with SIRPα to examine how targeting SIRPα affects bacterial survival and immune evasion. The findings will advance our understanding of bacterial infection mechanisms and open new avenues for combatting invasive disease.
Objective
Group B Streptococcus (GBS), or Streptococcus agalactiae, is the leading cause of sepsis and meningitis in human neonates and an emerging cause of invasive disease in adults. The detection of antibody-opsonised bacteria by phagocytic cells, like macrophages, elicits the ‘Eat Me’ signal that provides a critical arm of the host immune defence. Notably, bacterial pathogens often have immune evasion strategies to escape these processes. However, not all immune evasion mechanisms are understood for GBS and bacterial pathogens. Since bacterial pathogens often target specific cellular receptors, the host lab has performed a novel high-throughput screening of 1500 human cellular receptors for their interaction with GBS to uncover new host-pathogen interactions. This analysis revealed that the top hit is an inhibitory receptor called SIRPα expressed on macrophages. SIRPα detects CD47 on healthy cells to prevent macrophages from phagocytosing them. This is known as the ‘Don't Eat Me’ mechanism. Here, I hypothesise that bacterial pathogens like GBS interact with SIRPα to hijack the ‘Don’t Eat Me’ signal and evade macrophage phagocytosis and killing. I will use GBS as a study system. My objectives are to 1) use biochemical and structural approaches to define the GBS interaction with SIRPα, and use sophisticated genetic mutagenesis approaches to generate isogenic GBS strains that do not interact with SIRPα, 2) use cell and tissue infection models to determine the functional consequences of GBS targeting SIRPα. Overall, I will uncover a novel immune evasion strategy of GBS and establish whether pathogenic bacteria hijack SIRPα for immune evasion. More broadly, I will establish for the first time that our new high-throughput screening approach can uncover novel bacteria-human receptor interactions that have functional consequences in bacterial infection biology.
Fields of science (EuroSciVoc)
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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.
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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(opens in new window) HORIZON-MSCA-2025-PF
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SW7 2AZ London
United Kingdom
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