POST-DOCTORAL POSITION IN IMMUNOLOGY OPEN AT CR2TI

Our team scientific activity is committed to basic and translational research and aims at better understanding the role of Mononuclear Phagocytes (MNP) in inflammatory diseases and in host-virus interactions in the context of transplantation and immunodepression in order to identify new cellular and molecular therapeutic targets. We further developed new functional genomic approaches to better characterize MNP diversity and their role in immunopathology. We showed that the C-type Lectin receptor CLEC-1 acts in MNPs as an immune checkpoint during sterile inflammation (Lopez-Robles et al. Blood Adv 2017) (patent EP16306381). We now aim to study in depth the molecular mechanisms of the CLEC-1 checkpoint in mouse and human MNP in immunopathology by using functional genomics approaches. Pneumonia is currently a major cause of morbidity and mortality worldwide. To date, the most common treatments for pneumonia are antibiotics or antiviral drugs. However, these pathogen-targeted therapies fail to produce favorable results in 10-30% of patients, indicating that additional host-targeted approaches are needed to complement existing therapies. Sepsis causes inflammation and high susceptibility to nosocomial pneumonia by inducing immune defects collectively known as immunosuppression which is notably related to the emergence of myeloid suppressor cells. Our team 1 of CR2TI specialized in MNPs and immunotherapy has previously identified the CLEC-1 receptor expressed by myeloid cells, as a receptor acting as an immune checkpoint. Our team has hypothesized in collaboration with CR2TI team 6, specialized in the impact of inflammation on pulmonary homeostasis, that blocking CLEC-1 may help restore the functions of myeloid cells in patients with pneumonia. Thus, CLEC-1 might represent an original and attractive target to prevent persistent myeloid alterations and deleterious consequences in patients with pneumonia. We propose to 1) decipher the role of CLEC-1 in myeloid cell dysfunction and immune reprogramming during pneumonia by spectral cytometry and scRNA-seq experiments, 2) study CLEC-1 blockade in pre-clinical animal models, and 3) evaluate the clinical relevance of CLEC-1 by studying pneumonia patient samples.