Role of Matrix Metalloproteinase 10 in modulating immunopathology, inflammation, and tissue integrity during murine Leishmania major infection 2509

Abstract Description Leishmania major causes cutaneous leishmaniasis in endemic regions of Africa, the Middle East, and Central Asia. While Th1-mediated immunity is needed for L. major control, chronic infection can lead to prolonged lesions and immunopathological complications. Matrix metalloproteinase 10 (MMP10) is expressed by macrophages and keratinocytes in response to injury and infection. Although its functions are not well stablished, mostly of documented functions of MMP10 are limited to effects on macrophage activity that, in turn, affect macrophage activation status and persistence, tolerance, and their ability to degrade ECM. Hence, we investigated the role of MMP10 in L. major immunopathology. Wild-type (WT) and Mmp10–/– mice (C57BL/6N) were infected in the ear and analyzed for inflammation, collagen deposition, cell infiltration, and chemokine expression at 28 days post infection. Compared to WT mice, Mmp10–/– mice showed reduced inflammation in infected ears yet similar parasite burdens. Additionally, Mmp10–/– mice had increased collagen deposition and more intact tissue structure. Although lesion size and neutrophil infiltration were lower in Mmp10–/– mice, CCL2 expression was elevated, alongside decreased caspase 3 and 7 activity in infected and uninfected macrophages. Thus, MMP10 significantly influences immunopathology in L. major infections, exacerbating inflammation and tissue disruption, while also impacting immune cell recruitment and survival in infected tissue. Funding Sources NIH 236971 Authors: Diogo Valadares, Hengameh Sadeghi, William C Parks, Suzanne L Cassel, Fayyaz S Sutterwala. Departments of Medicine and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, United States. Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)