Plasmodium sporozoites are transmitted by Anopheles mosquitoes and infect hepatocytes, where a single sporozoite replicates into thousands of merozoites inside a parasitophorous vacuole. The nature of the Plasmodium-host cell interface, as well as the interactions occurring between these two organisms, remains largely unknown. Here we show that highly dynamic hepatocyte actin reorganization events occur around developing Plasmodium berghei parasites inside human hepatoma cells. Actin reorganization is most prominent between 10 to 16 hours post infection and depends on the actin severing and capping protein, gelsolin. Live cell imaging studies also suggest that the hepatocyte cytoskeleton may contribute to parasite elimination during Plasmodium development in the liver.
References
[1]
Schaible U, Haas A (2009) Intracellular Niches of Microbes: A Pathogens Guide Through the Host Cell.
[2]
Patel JC, Galan JE (2005) Manipulation of the host actin cytoskeleton by Salmonella–all in the name of entry. Curr Opin Microbiol 8: 10–15.
[3]
Munter S, Way M, Frischknecht F (2006) Signaling during pathogen infection. Sci STKE 2006: re5.
[4]
Elliott DA, Clark DP (2000) Cryptosporidium parvum induces host cell actin accumulation at the host-parasite interface. Infect Immun 68: 2315–2322.
[5]
Frenal K, Soldati-Favre D (2009) Role of the parasite and host cytoskeleton in apicomplexa parasitism. Cell Host Microbe 5: 602–611.
[6]
von Schubert C, Xue G, Schmuckli-Maurer J, Woods KL, Nigg EA, et al. (2010) The transforming parasite Theileria co-opts host cell mitotic and central spindles to persist in continuously dividing cells. PLoS Biol 8:
[7]
Gonzalez V, Combe A, David V, Malmquist NA, Delorme V, et al. (2009) Host cell entry by apicomplexa parasites requires actin polymerization in the host cell. Cell Host Microbe 5: 259–272.
[8]
Coppens I, Dunn JD, Romano JD, Pypaert M, Zhang H, et al. (2006) Toxoplasma gondii sequesters lysosomes from mammalian hosts in the vacuolar space. Cell 125: 261–274.
[9]
Oh SS, Voigt S, Fisher D, Yi SJ, LeRoy PJ, et al. (2000) Plasmodium falciparum erythrocyte membrane protein 1 is anchored to the actin-spectrin junction and knob-associated histidine-rich protein in the erythrocyte skeleton. Mol Biochem Parasitol 108: 237–247.
[10]
Pei X, Guo X, Coppel R, Mohandas N, An X (2007) Plasmodium falciparum erythrocyte membrane protein 3 (PfEMP3) destabilizes erythrocyte membrane skeleton. J Biol Chem 282: 26754–26758.
[11]
Millholland MG, Chandramohanadas R, Pizarro A, Wehr A, Shi H, et al. (2011) The malaria parasite progressively dismantles the host erythrocyte cytoskeleton for efficient egress. Mol Cell Proteomics.
[12]
Bano N, Romano JD, Jayabalasingham B, Coppens I (2007) Cellular interactions of Plasmodium liver stage with its host mammalian cell. Int J Parasitol 37: 1329–1341.
[13]
Sturm A, Graewe S, Franke-Fayard B, Retzlaff S, Bolte S, et al. (2009) Alteration of the parasite plasma membrane and the parasitophorous vacuole membrane during exo-erythrocytic development of malaria parasites. Protist 160: 51–63.
[14]
Yam PT, Theriot JA (2004) Repeated cycles of rapid actin assembly and disassembly on epithelial cell phagosomes. Mol Biol Cell 15: 5647–5658.
[15]
Merrifield CJ, Moss SE, Ballestrem C, Imhof BA, Giese G, et al. (1999) Endocytic vesicles move at the tips of actin tails in cultured mast cells. Nat Cell Biol 1: 72–74.
[16]
Taunton J (2001) Actin filament nucleation by endosomes, lysosomes and secretory vesicles. Curr Opin Cell Biol 13: 85–91.
[17]
Anes E, Kuhnel MP, Bos E, Moniz-Pereira J, Habermann A, et al. (2003) Selected lipids activate phagosome actin assembly and maturation resulting in killing of pathogenic mycobacteria. Nat Cell Biol 5: 793–802.
[18]
Albuquerque SS, Carret C, Grosso AR, Tarun AS, Peng X, et al. (2009) Host cell transcriptional profiling during malaria liver stage infection reveals a coordinated and sequential set of biological events. BMC Genomics 10: 270.
[19]
Sun HQ, Yamamoto M, Mejillano M, Yin HL (1999) Gelsolin, a multifunctional actin regulatory protein. J Biol Chem 274: 33179–33182.
[20]
Johnston SA, May RC (2010) The human fungal pathogen Cryptococcus neoformans escapes macrophages by a phagosome emptying mechanism that is inhibited by Arp2/3 complex-mediated actin polymerisation. PLoS Pathog 6:
[21]
Hybiske K, Stephens RS (2007) Mechanisms of host cell exit by the intracellular bacterium Chlamydia. Proc Natl Acad Sci U S A 104: 11430–11435.
[22]
Ma H, Croudace JE, Lammas DA, May RC (2007) Direct cell-to-cell spread of a pathogenic yeast. BMC Immunol 8: 15.
[23]
Mostowy S, Bonazzi M, Hamon MA, Tham TN, Mallet A, et al. (2010) Entrapment of intracytosolic bacteria by septin cage-like structures. Cell Host Microbe 8: 433–444.
[24]
Kobayashi I, Hakuno H (2003) Actin-related defense mechanism to reject penetration attempt by a non-pathogen is maintained in tobacco BY-2 cells. Planta 217: 340–345.
[25]
Tian M, Chaudhry F, Ruzicka DR, Meagher RB, Staiger CJ, et al. (2009) Arabidopsis actin-depolymerizing factor AtADF4 mediates defense signal transduction triggered by the Pseudomonas syringae effector AvrPphB. Plant Physiol 150: 815–824.
[26]
Mendes AM, Schlegelmilch T, Cohuet A, Awono-Ambene P, De Iorio M, et al. (2008) Conserved mosquito/parasite interactions affect development of Plasmodium falciparum in Africa. PLoS Pathog 4: e1000069.
[27]
Ray K, Bobard A, Danckaert A, Paz-Haftel I, Clair C, et al. (2010) Tracking the dynamic interplay between bacterial and host factors during pathogen-induced vacuole rupture in real time. Cell Microbiol 12: 545–556.
Franke-Fayard B, Trueman H, Ramesar J, Mendoza J, van der Keur M, et al. (2004) A Plasmodium berghei reference line that constitutively expresses GFP at a high level throughout the complete life cycle. Mol Biochem Parasitol 137: 23–33.
[30]
Moffat J, Grueneberg DA, Yang X, Kim SY, Kloepfer AM, et al. (2006) A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen. Cell 124: 1283–1298.
[31]
Prudencio M, Rodrigues CD, Hannus M, Martin C, Real E, et al. (2008) Kinome-wide RNAi screen implicates at least 5 host hepatocyte kinases in Plasmodium sporozoite infection. PLoS Pathog 4: e1000201.