Characterization of a new intermediate macrophage subpopulation : SDC-1 positive SPM-like macrophages possess immunosuppressive functions in early mesotheliomagenic responses to carbon nanotubes

Malignant mesothelioma is a disease caused by inhalation of needle-like shaped particles and whose pathogenesis is not yet fully elucidated. A long-lasting general inflammation caused by persistent mesotheliomagenic particles is not sufficient to explain mesothelioma onset. Indeed, challenging data have shown that mesothelioma occurs without chronic inflammation. Our research team previously helped to discover that, beside inflammation, particles such as silica also induce a selective, rapid and sustained accumulation of immunosuppressive cells (regulatory T lymphocytes, myeloid derived suppressive cells and M2/regulatory macrophages) participating to fibrogenesis. To determine whether carcinogenic particles such as asbestos and carbon nanotubes (CNT) also elicit immunosuppressive responses, we investigated the impact of these particles on macrophage turnover, phenotype and immunosuppressive activity. With that purpose, we intraperitoneally injected mesotheliomagenic CNT-7 (needle-like, Mitsui & Co) and non-mesotheliomagenic CNT-T (tangled, Nagoya University) particles in Wistar rats and compared the effects on peritoneal macrophage subpopulations. We showed that macrophages die very rapidly in the attempt to phagocyte mesotheliomagenic CNT. They are later replenished by monocytic-derived small peritoneal macrophages (SPM-like macrophages) possessing comparable immunosuppressive functions and signatures to Tumor-Associated Macrophages (TAM), which infiltrate mesothelioma and block T cell antitumor activities. Early immunosuppressive SPM-like macrophages express and release the shed form of the immunoregulatory syndecan-1 glycoprotein, which could explain the immunosuppression that they exert on T cells. Non-mesotheliomagenic peritoneal responses induced by CNT-T are, in contrast, characterized by a recruitment of self-proliferating large peritoneal macrophages (LPM-like macrophages) that correspond to homeostatic macrophages without immunosuppressive activity. Our o
(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 2021