Figure 1.

Schematic view of colonization, invasion and evasion mechanisms displayed by pathogenic Leptospira. Leptospires can penetrate the host via breached skin or intact mucosa, taking advantage of many surface exposed proteins that are able to interact with a broad range of host components, including the extracellular matrix (ECM) components and glycosaminoglycans (GAGs). During the invasion process, leptospires can directly bind to ECM components and cell receptors, as cadherins, the latter favoring cell-cell integrity disruption (center). Leptospires interact with host plasminogen (PLG) (top and center) and induce the endothelial secretion of urokinase-type PLG activator (uPA), which in turn converts leptospires-bound PLG to its active form, plasmin (PLA). The latter, a broad-spectrum serine protease, is capable of degrading ECM components and immune mediators, as IgG and C3b, reducing opsonophagocytosis (top). One of the host mechanisms to block pathogen dissemination to other sites after endothelial lesion is the formation of fibrin clot, as a result of fibrinogen (Fg) cleavage by thrombin. In addition to Fg degradation by PLA, pathogenic Leptospira can also bind both Fg and thrombin, causing a bilateral obstruction of the fibrin clot reaction, favoring the dissemination step (left bottom), in association with ECM degradation by endogenous proteases and surface-associated PLA (center). Once in the bloodstream, leptospires must overcome one of the first lines of host defense, the complement, and this is achieved by a multitude of mechanisms, including binding to the negative complement regulators Factor H (FH) and C4 binding protein (C4BP), which participate in the degradation of C3b and C4b, respectively. Binding to terminal components C7, C8, C9 and vitronectin, would decrease membrane attack complex (MAC) formation (right bottom). Taken together, it is anticipated that these mechanisms will facilitate invasion and dissemination of Leptospira through the hosts.