Abstract
Intracellular pathogens have numerous strategies for effective dissemination within the host. Many intracellular pathogens first infect leukocytes, which they use as a vehicle to transport them to target organs. Once at the target organ, intracellular parasite Toxoplasma gondii can cross the capillary wall in extracellular form by infecting endothelial cells. However, after egression from leukocytes, extracellular parasites face the risk of host immune attack. In this study, observation of infected mouse organs, using a method that renders tissue transparent, revealed that adhesion of tachyzoite-infected leukocytes to endothelial cells triggers immediate egression of the parasite. This signal enables the parasite to time egression from its vehicle leukocyte to coincide with arrival at a target organ, minimizing the opportunity for immune attack during the transition from a vehicle leukocyte to capillary endothelial cells.
Highlights
Toxoplasma gondii is an obligate intracellular parasite responsible for congenital infections, abortion and opportunistic diseases in immunodeficient individuals
We demonstrated that tachyzoite-infected leukocytes in the general circulation remain in the lung by effective adhesion to lung endothelial cells and that this adhesion triggers tachyzoite egression from the vehicle leukocyte
It had been thought that extravasation of these infected leukocytes transfers the microorganisms from the blood to solid organs beyond the blood vessel wall, in a “Trojan horse”-like manner[23,24,25]
Summary
Toxoplasma gondii is an obligate intracellular parasite responsible for congenital infections, abortion and opportunistic diseases in immunodeficient individuals. It has been reported that T. gondii tachyzoites infect leukocytes in the lamina propria extravascular space[4, 5] and that T. gondii-infected leukocytes in the general circulation transport the tachyzoites to the peripheral organs[6,7,8]. For effective transition from leukocytes in the general circulation to solid organs, T. gondii must egress from the vehicle leukocyte near to the target organ thereby allowing egressed extracellular parasites to immediately enter target cells. We revealed that T. gondii senses the arrival of their vehicle leukocytes at the target organs and immediately egresses out from the host leukocyte. As an obligate intracellular parasite with limited capacity for extracellular survival, T. gondii does not randomly egress out from its vehicle cell but rather senses the location within the host body and times egression to maximize its chances of survival
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