UNASSIGNED: Parasites of the @entity281 and survive within macrophages by inhibiting several microbicidal molecules, such as @entity842 and pro-inflammatory cytokines. In this context, various species of Leishmania have been reported to inhibit or reduce the production of @entity1356 both in vitro and in vivo. However, the mechanism whereby Leishmania parasites are able to affect @entity1356 production and secretion by macrophages is still not fully understood. Dependent on the stimulus at hand, the maturation of @entity1356 is facilitated by different inflammasome complexes. The @entity5704 inflammasome has been shown to be of pivotal importance in the detection of danger molecules such as @entity4532 , @entity3440 and malarial hemozoin, (HZ) as well as infectious agents. In the present work, we investigated whether Leishmania parasites modulate @entity5704 inflammasome activation. Using @entity4515 -differentiated THP-1 cells, we demonstrate that @entity281 effectively inhibits macrophage @entity1356 production upon stimulation. In this context, the expression and activity of the metalloprotease @entity41579 - a critical virulence factor expressed by all infectious Leishmania species - is a prerequisite for a Leishmania-mediated reduction of @entity1356 secretion. Accordingly, L. mexicana, purified @entity41579 and @entity41579 -containing exosomes, caused the inhibition of macrophage @entity1356 production. Leishmania-dependent suppression of @entity1356 secretion is accompanied by an inhibition of reactive @entity26 species (ROS) production that has previously been shown to be associated with @entity5704 inflammasome activation. The observed loss of ROS production was due to an @entity73 . Furthermore, ROS-independent inflammasome activation was inhibited, possibly due to an observed @entity41579 -dependent cleavage of inflammasome and inflammasome-related proteins. Collectively for the first time, we herein provide evidence that the protozoan parasite Leishmania, through its surface metalloprotease @entity41579 , can significantly inhibit @entity5704 inflammasome function and @entity1356 production.

PKC/ROS-Mediated XXXX Inflammasome Activation Is Attenuated by Leishmania Zinc-Metalloprotease during Infection.

@entity4532 :: ('MESH:C537431', 'Disease') :: ['inorganic crystals like asbestos'] @entity5704 :: ('114548', 'Gene') :: ['NLRP3'] @entity1356 :: ('3553', 'Gene') :: ['IL-1b'] @entity73 :: ('MESH:D003072', 'Disease') :: ['impaired PKC-mediated protein phosphorylation'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity4515 :: ('CHEBI:60755', 'Chemical') :: ['PMA'] @entity281 :: ('MESH:D007239', 'Disease') :: ['Leishmania genus infect', 'Leishmania infection'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity3440 :: ('MESH:D012822', 'Chemical') :: ['silica'] @entity41579 :: ('89782', 'Gene') :: ['GP63']
@entity5704 :: (114548,Gene) :: ['NLRP3']
