Functional paradox in host–pathogen interaction dictates the fate of parasites

The interactions between the protozoan parasite Leishmania and host macrophages are complex and involve several paradoxical functions that are meant for protection of the host but exploited by the parasite for its survival. The initial interaction of the parasite surface molecules with the host-cell receptors plays a major role in the final outcome of the disease state. While the interactions between macrophages and a virulent strain of Leishmania trigger a cascade of cell-signaling events leading to immunosuppression, the interaction with an avirulent strain triggers host-protective immune effector functions. Thus, an incisive study on Leishmania–macrophage interactions reveals functional paradoxes that highlight the concept of ‘relativity in parasite virulence’. Using Leishmania infection as a model, we propose that virulence of a pathogen and the resistance (or susceptibility) of a host to the pathogen are relative properties that equate to combinatorial functions of several sets of molecular processes.