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Structure and Function of the Parasitophorous Vacuole in Eimeria Species R[ Entzeroth \ F[R[ Mattig\ R[ Werner!Meier

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Structure and Function of the Parasitophorous Vacuole in Eimeria Species R[ Entzeroth \ F[R[ Mattig\ R[ Werner!Meier International Journal for Parasitology 17 "0887# 0904Ð0907 Structure and function of the parasitophorous vacuole in Eimeria species R[ Entzeroth\ F[R[ Mattig\ R[ Werner!Meier Institute of Zoology\ University of Technology Dresden\ Mommsenstra)e 02\ 90951 Dresden\ Germany Received 0 December 0886^ accepted 09 March 0887 Abstract The intracellular life!cycle stages of Eimeria are located in the host cell within a membrane!bound parasitophorous vacuole[ The invasion process and the formation of the parasitophorous vacuole are mediated by characteristic organelles within the apical complex[ During invasion\ the parasitophorous!vacuole membrane is manipulated by the parasite and functions later in the development cycle as a molecular sieve\ allowing the exchange of metabolites between parasite and host cell[ Unlike the cyst!forming coccidia\ there is little evidence of parasitophorous!vacuole membrane transformation in the later stages of the lifecycle of Eimeria species[ Compared with the human pathogens Plasmodium and Toxoplasma\ rather little is known about the parasitophorous vacuole and parasitophorous!vacuole membrane of animal pathogens of the genus Eimeria[ Þ 0887 Australian Society for Parasitology[ Published by Elsevier Science Ltd[ Keywords] Parasitophorous vacuole "PV#^ Eimeria^ Parasite 0[ Introduction PV membrane "PVM# is formed during invasion of the motile stages of Eimeria parasites "sporozoites Parasites of the genus Eimeria are obligatory and merozoites#[ The invasion of Eimeria spp[ is an intracellular parasites mostly of intestinal cells\ active process and resembles closely that in other although some live in other cells and:or organs of related species of Apicomplexa "Toxoplasma\ Plas! invertebrates and vertebrates[ Coccidiosis of dom! modium#[ The PVM serves to protect the parasite estic animals\ cattle and chickens is due to infection against lysis by the host cell\ but also constitutes a with di}erent Eimeria spp[ and causes considerable barrier between the host!cell metabolites and the economic losses[ The animal!breeding industry parasite that depends on them[ Since Eimerian spends millions of dollars each year on measures to parasites do not form cysts\ modi_cation of the control coccidiosis\ mainly anticoccidial drugs[ PVM is usually not observed[ The intracellular life!cycle stages of Eimeria para! sites\ including merozoites\ schizonts "meronts# and gamonts\ are located within the host cell in a mem! 1[ Organelles involved with invasion and brane!bound parasitophorous vacuole "PV# ð0Ł[ The parasitophorous!vacuole formation The invasion process of Eimeria by the motile Corresponding author[ Tel[] 9240:352! 6425^ fax] 9240:352! zoites is active\ and characteristic organelles from 6130[ within the apical complex "conoid\ polar rings\ mic! S9919!6408:87 ,08[99¦9[99 Þ 0887 Australian Society for Parasitology[ Published by Elsevier Science Ltd[ Printed in Great Britain PII] S9919!6408"87#99968!3 0905 R[ Entzeroth et al[ : International Journal for Parasitolo`y 17 "0887# 0904Ð0907 ronemes\ rhoptries and dense granules# are of func! cells infected with E[ nieschulzi have shown that tional importance[ The function of the conoid and molecules of up to 749 Da can pass the PVM\ while polar rings is so far unknown[ Micronemes promote molecules of 09 999 Da are excluded from the PV the attachment of parasites to the potential host ð07Ł[ Similar results have been obtained in Plas! cells ð1Ł[ The zoites come into contact with the epi! modium[ The experiments give evidence that the thelial cell ð2\ 3Ł and micronemes secrete their pro! PVM may function as a molecular sieve[ Postulated tein contents\ which have been characterised ð1\ 4Ł[ pores across the PVM probably provide nutritional The known sequences of some microneme proteins channels that allow the passive transfer of mol! ð5Ł are very similar within the di}erent apic! ecules to the parasite[ omplexan species and indicate a common function[ The function of duct!like structures within There is also evidence that\ as well as the attachment infected host cells\ marked by rhoptry!speci_c mAb function\ micronemes are involved in motility since ð08Ł\ is not yet known[ These structures resemble the microneme knock!out mutants in Plasmodium lose postulated {{parasitophorous duct|| in Plasmodium the ability to move and invade host cell ð6Ł[ Rhop! ð19Ð11Ł\ which was claimed to allow the di}usion tries may have functions in the initial process of even of macromolecules from the extracellular med! PV formation during invasion ð7\ 8Ł and have been ium into the parasitophorous vacuole[ Obviously\ shown to discharge their contents through a duct the two models of transport into the PV are essen! into the forming parasitophorous vacuole[ In Tox! tially incompatible] if a direct connection "{{duct||# oplasma at least 09 rhoptry proteins have been existed together with pores in the PVM\ the host identi_ed ð09Ł and some of these proteins "ROP 1\ cell would leak low molecular weight solutes into 2\ 3# are stably associated with the membrane lining the extracellular space[ the PVM[ In Eimeria species\ rhoptry proteins have The PVM in Toxoplasma!infected cells is fusion been characterised in sporozoites of Eimeria tenella incompetent for lysosomes\ protecting the parasite ð00\ 01Ł and merozoites of Eimeria nieschulzi ð02Ł[ from lytic enzymes ð12\ 13Ł[ No experiments have Using rhoptry!speci_c antibodies\ rhoptry proteins been performed yet to show fusion incompetence from E[ tenella were shown to be associated with for the PVM in Eimeria!infected cells[ the PVM ð00\ 01Ł and in E[ nieschulzi a 11!kDa rhoptry protein was shown to be exocytosed into the PV at invasion ð02Ł[ The total protein content 3[ Modi_cation of the parasitophorous vacuole of rhoptries of Eimeria spp[ is very heterogeneous during the life!cycle of Eimeria ð03Ł and the protein contents may di}er between rhoptries of sporozoites and merozoites from the In cyst!forming Coccidia\ the PV is modi_ed same species\ as indicated by rhoptry!speci_c anti! shortly after invasion[ In Toxoplasma an intra! bodies ð02\ 03Ł[ Dense granules are discharged after vacuolar network is formed with which secreted invasion in the cyst!forming Coccidia "Sarcocystis\ proteins of dense granules become associated ð14Ł[ Toxoplasma# and contribute to the modi_cation of In Sarcocystis\ bradyzoites escape from the primary the PV and PVM in these species ð04Ł[ There is only PV and a secondary PV derived from host!cell little evidence that dense granules exist in Eimeria endoplasmic reticulum is formed and dense gran! species ð05Ł and the function of this organelle is not ules are exocytosed ð15Ł[ yet known[ There is little evidence of transformation of the PV in Eimeria[ The presence and exocytosis of dense granules have been postulated in E[ tenella ð05Ł and 2[ Transport across the parasitophorous!vacuole Eimeria papillata ð16Ł[ Electron!dense material has membrane been reported in the PV of several Eimeria species ð17Ð29Ł[ Intravacuolar tubules are peculiar struc! The PVM in Toxoplasma is permeable for tures within the PV of Eimeria maxima mac! charged and uncharged molecules of less than rogamonts ð20Ł[ In E[ nieschulzi schizonts\ the PVM 0399 Da ð06Ł[ Microinjection experiments in host bears {{microvilli|| protruding into the PV ð23Ł[ R[ Entzeroth et al[ : International Journal for Parasitolo`y 17 "0887# 0904Ð0907 0906 After di}erentiation of merozoites in schizonts\ ð7Ł Joiner KA\ Beckers CJM\ Bermudes D\ Ossorio PN\ Sch! merozoites become active and leave the par! wab JC\ Dubremetz JF[ Structure and function of the par! asitophorous vacuole membrane surrounding Toxoplasma asitophorous vacuole[ The mechanism of merozoite gondii[ Ann NY Acad Sci 0883^629]0Ð7[ release is poorly known\ and may be active or ð8Ł Carruthers VB\ Sibley LD[ Sequential protein secretion passive[ Parasite proteases may be involved also in from three distinct organelles of Toxoplasma gondii Eimeria spp[ as documented in Plasmodium ð21\ 22Ł[ accompanies invasion of human _broblasts[ Eur J Cell Biol 0886^62]003Ð012[ ð09Ł Leriche MA\ Dubremetz JF[ Characterization of the pro! tein contents of rhoptries and dense granules of Toxoplasma 4[ Conclusion gondii tachyzoites by subcellular fractionation and mon! oclonal antibodies[ Mol Biochem Parasitol 0880^34]138Ð The PV is a crucial structure in the life!cycle of 159[ Coccidia\ although there are a few exceptions where ð00Ł Greif G\ Entzeroth R[ Eimeria tenella] localisation of rhop! the PV is absent "Theileria\ Babesia\ certain stages try antigens during parasiteÐhost cell interactions by a rhop! try!speci_c monoclonal antibody in PCK cell culture[ Appl of Sarcocystis#[ The PV is manipulated by the para! Parasitol 0885^26]142Ð148[ site and functions as a molecular sieve\ allowing the ð01Ł Greif G\ Entzeroth R[ Eimeria tenella] localization of cross! exchange of metabolites between parasite and host reacting epitopes in rhoptry\ nucleus and host cell nucleus cell[ Compared with the human pathogens Plas! during parasiteÐhost cell interactions by a monoclonal anti! modium and Toxoplasma\ rather little is known body in PCKC culture[ J Protozool Res 0884^4]065Ð075[ ð02Ł Rick B\ Dubremetz JF\ Entzeroth R[ A merozoite speci_c about the animal pathogens of the genus Eimeria[ 11 kDa rhoptry protein of the coccidium Eimeria nieschulzi Understanding of the formation\ modi_cation and "Sporozoa\ Coccidia# is exocytosed in the parasitophorous function of the PV would facilitate the development vacuole upon host cell invasion[ In press[
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