Plasmodium exoerythrocytic parasites redirect trafficking of human proteins to the parasitophorous vacuole

Calla, J.; Mittal, N.; LaMonte, G.; Liffner, B.; Godinez-Macias, K.; Carolino, K.; Walker, G. T.; Zou, B. Y.; Paytas, E.; Guerra, L.; Tong-Rios, C.; Campo, B.; Vinetz, J. M.; Gamboa, D.; Raffatellu, M.; Absalon, S.; Winzeler, E.

doi:10.1101/2022.11.22.517223

bioRxiv · 10.1101/2022.11.22.517223

Plasmodium exoerythrocytic parasites redirect trafficking of human proteins to the parasitophorous vacuole

Calla, J.·Mittal, N.·LaMonte, G.·Liffner, B.·Godinez-Macias, K.·Carolino, K.·Walker, G. T.·Zou, B. Y.·Paytas, E.·Guerra, L.·Tong-Rios, C.·Campo, B.·Vinetz, J. M.·Gamboa, D.·Raffatellu, M.·Absalon, S.·Winzeler, E.

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Abstract

Changes in host cell morphology and transcription after apicomplexan parasite infection have long been noted, but there have been few studies of the functional consequences of host cell remodeling. Here we show, using time-dependent immunofluorescence microscopy of multiple human cell lines (HepG2, HC-04, Huh7.5.1 and primary human hepatocytes), infected with multiple Plasmodium species (Plasmodium berghei, P. falciparum and P. vivax (hypnozoites and schizonts)), and antibodies to multiple human proteins (HsNR4A3, HsMUC13, HsGOLGA8A, HsCGA, HsBiP, HsCXCL2), that human protein trafficking is extensively modified in Plasmodium infected cells. Using conventional as well as ultrastructure expansion microscopy we show that newly-synthesized human proteins are trafficked to the parasitophorous vacuole instead of the infected-cell plasma membrane, nucleus or extracellular space. Universal redirection of human signaling proteins cells the parasitophorous vacuole may provide a mechanistic explanation for how apicomplexan parasites can block host cells response to infection.

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Calla, J., Mittal, N., LaMonte, G., Liffner, B., Godinez-Macias, K., Carolino, K., Walker, G. T., Zou, B. Y., Paytas, E., Guerra, L., Tong-Rios, C., Campo, B., Vinetz, J. M., Gamboa, D., Raffatellu, M., Absalon, S., Winzeler, E.. 2022-11-23. Plasmodium exoerythrocytic parasites redirect trafficking of human proteins to the parasitophorous vacuole. https://doi.org/10.1101/2022.11.22.517223

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