Echeverría-Valencia, Gabriela, Silva-Miranda, Mayra, Ekaza, Euloge, Vallecillo, Antonio, Parada, Cristina, Sada-Ovalle, Isabel, Altare, Frédéric, Espitia, Clara, Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México (UNAM), Consejo Nacional de Ciencia y Tecnología [Mexico] (CONACYT), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Facultad de Ciencias Agropecuarias [Cuanca, Ecuador], Instituto Nacional de Enfermedades Respiratorias [México, Mexico], Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and ALTARE, Frédéric
International audience; Plasminogen and plasmin are fundamental components of the fibrinolytic system that interact with microorganisms generating different immunopathological effects. The molecules of Mycobacterium tuberculosis inter-playing with plasminogen have already been identified and characterized. In this work, we studied the effects of plasmin(ogen) bound to Mycobacterium bovis Calmette-Guérin (BCG) on phagocytosis in THP1 macrophages as well as in granuloma formation and development on in vitro human granuloma model. For this purpose, BCG was coated with plasminogen and plasmin, obtained after activation of zymogen by tissue plasminogen activator. The results showed a significant reduction in the number of bacteria phagocytosed by macrophages in presence of plasminogen or plasmin on BCG surface. On the other hand, at 3 days BCG/plasminogen/plasmin induced an increase granuloma numbers with respect to those induced by uncoated bacteria. BCG/plasminogen/environ-ments also showed a significant increase of IL-6 secretion. At 7 days, a reduced number of granulomas and an increased number of bacteria was observed with respect to uncoated BCG environment. Altogether, these results showed that plasmin(ogen) on the mycobacterial surface affects phagocytosis, granuloma development and the cytokine context, thus resulting in an increased number of bacteria in granulomas.