Evaluate the immune checkpoint CLEC-1 as a therapeutic target for sepsis. – CLIPS

Pneumonia is a world-wide major cause of morbidity and mortality. To date, the most common treatments of pneumonia are antibiotics or antiviral drugs. However, these pathogens-targeted therapies do not result in favorable outcomes for 10 to 30% of patients, indicating that additional host-targeted approaches are required to complement existing therapeutics. Sepsis causes inflammation and elevated susceptibility to hospital-acquired pneumonia by inducing immune defects collectively known as critical illness-related immunosuppression with the emergence of suppressive immature myeloid cells. Based on the immuno-suppressive effects of the innate C-type Lectin receptors (CLR) on myeloid cell-activation, development of antagonists targeting these receptors may represent a scheme of promising to restore myeloid cell functions in such immuno-paralyzed patients. The consortium raises the hypothesis that blockade of the CLR CLEC-1 has the potential to reset myeloid programming during inflammation and enhance outcomes of patients with pneumonia. The consortium gathering complementary expertise on CLEC-1 and on the impact of inflammation on myeloid cells in pneumonia proposes a translational project to: 1) Decipher the role of CLEC-1 in myeloid-cell dysfunction and immune reprogramming during pneumonia 2) Provide the preclinical proof of concept of CLEC-1 blockade to recover normal immune functions after pneumonia 3) Unravel the clinical relevance of CLEC-1 by studying samples collected in patients with pneumonia. At the end of this project, the consortium will be able to present CLEC-1 as an original and attractive therapeutic tool to pave the way for clinical trials to prevent the persistent myeloid alterations and the deleterious outcomes of patients with pneumonia.