TY - JOUR
T1 - Interaction of mycobacteria with Plasmin(ogen) affects phagocytosis and granuloma development
AU - Echeverría-Valencia, Gabriela
AU - Silva-Miranda, Mayra
AU - Ekaza, Euloge
AU - Vallecillo, Antonio J.
AU - Parada, Cristina
AU - Sada-Ovalle, Isabel
AU - Altare, Frédéric
AU - Espitia, Clara
N1 - Publisher Copyright:
© 2019
PY - 2019/7
Y1 - 2019/7
N2 - Plasminogen and plasmin are fundamental components of the fibrinolytic system that interact with microorganisms generating different immunopathological effects. The molecules of Mycobacterium tuberculosis interplaying 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/environments 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.
AB - Plasminogen and plasmin are fundamental components of the fibrinolytic system that interact with microorganisms generating different immunopathological effects. The molecules of Mycobacterium tuberculosis interplaying 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/environments 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.
KW - BCG
KW - Fibrinolytic system
KW - Granuloma
KW - Mycobacterium
KW - Plasmin
KW - Plasminogen
KW - Tuberculosis
UR - https://www.scopus.com/pages/publications/85066758429
U2 - 10.1016/j.tube.2019.05.008
DO - 10.1016/j.tube.2019.05.008
M3 - Artículo
C2 - 31378266
AN - SCOPUS:85066758429
SN - 1472-9792
VL - 117
SP - 36
EP - 44
JO - Tuberculosis
JF - Tuberculosis
ER -
