Hostname: page-component-8448b6f56d-cfpbc Total loading time: 0 Render date: 2024-04-18T04:37:26.063Z Has data issue: false hasContentIssue false
  • English
  • Français

Plasmodium falciparum ookinete invasion of the midgut epithelium of Anopheles stephensi is consistent with the Time Bomb model

Published online by Cambridge University Press:  18 November 2004

L. A. BATON  and
L. C. RANFORD-CARTWRIGHT
L. A. BATON
Affiliation:
Division of Infection and Immunity, Institute of Biomedical and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, UK
L. C. RANFORD-CARTWRIGHT
Affiliation:
Division of Infection and Immunity, Institute of Biomedical and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, UK
Get access Rights & Permissions [Opens in a new window]

Abstract

Plasmodium falciparum gametocytes grown in vitro were fed through membrane feeders to laboratory-reared Anopheles stephensi mosquitoes. Intact midguts, including entire bloodmeal contents, were removed between 24 and 48 h post-bloodfeeding. Giemsa-stained histological sections were prepared from the midguts and examined by light microscopy. Contrary to previous reports, ookinetes were clearly visible within midgut epithelial cells, demonstrating intracellular migration across the midgut wall. Ookinetes entered epithelial cells through the lateral apical membrane at sites where 3 adjacent cells converged. There was no evidence for the existence of a morphologically distinct group of epithelial cells preferentially invaded by ookinetes. However, ookinete penetration was associated with significant morphological changes to invaded cells, including differential staining, condensation and fragmentation of the nucleus, vacuolization, loss of microvilli and various degrees of extrusion into the midgut lumen. Epithelial cells completely separated from the midgut wall were found within the midgut lumen. These cells were associated with invading parasites suggesting that ookinete penetration resulted in complete ejection of invaded cells from the midgut wall. Small clusters of morphologically altered midgut cells and invading parasites spanning the membranes of adjacent abnormal epithelial cells were observed, consistent with intracellular movement of ookinetes between neighbouring midgut cells. Extruded epithelial cells were also observed rarely in uninfected midguts. Epithelial cell extrusion, therefore, may be a general mechanism of tissue repair through which damaged cells are removed from the midgut wall rather than a parasite-specific response. These observations demonstrate that human malaria parasite infection of mosquitoes is consistent with, and provides further support for, the Time Bomb model of ookinete invasion of the mosquito midgut epithelium previously proposed for rodent malaria parasites.

Keywords

Anopheles stephensiookinetemidgut invasionparasite-vector interactionPlasmodium falciparumTime Bomb model
Type
Research Article
Information
Parasitology , Volume 129 , Issue 6 , December 2004 , pp. 663 - 676
Copyright
© 2004 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

BECKER-FELDMAN, H., MAIER, W. A. & SEITZ, H. M. ( 1985). Electron microscope observations on the pathology of the midgut epithelial cells of Anopheles stephensi after infection with Plasmodium yoelii nigeriensis. Tropical Medicine and Parasitology 36, 5–6.Google Scholar
BERTRAM, D. S. & BIRD, R. G. ( 1961). Studies on mosquito-borne viruses in their vectors. I. The normal fine structure of the midgut epithelium of the adult female Aedes aegypti (L.) and the functional significance of its modulation following a bloodmeal. Transactions of the Royal Society of Tropical Medicine and Hygiene 55, 404–423.CrossRefGoogle Scholar
BILLINGSLEY, P. F. ( 1990). The midgut ultrastructure of haematophagous insects. Annual Review of Entomology 35, 219–248.CrossRefGoogle Scholar
BROWN, M. R., CRIM, J. W. & LEA, A. O. ( 1986). FMRFamide- and pancreatic polypeptide-like immunoreactivity of endocrine cells in the midgut of a mosquito. Tissue and Cell 18, 419–428.CrossRefGoogle Scholar
BROWN, M. R., RAIKHEL, A. S. & LEA, A. O. ( 1985). Ultrastructure of midgut endocrine cells in the adult mosquito, Aedes aegypti. Tissue and Cell 17, 709–721.CrossRefGoogle Scholar
CANNING, E. U. & SINDEN, R. E. ( 1973). The organization of the ookinete and observations on nuclear division in oocysts of Plasmodium berghei. Parasitology 67, 29–40.CrossRefGoogle Scholar
CARTER, R., RANFORD-CARTWRIGHT, L. & ALANO, P. ( 1993). The culture and preparation of gametocytes of Plasmodium falciparum for immunochemical, molecular, and mosquito infectivity studies. Methods in Molecular Biology 21, 67–88.CrossRefGoogle Scholar
COCIANCICH, S. O., PARK, S. S., FIDOCK, D. A. & SHAHABUDDIN, M. ( 1999). Vesicular ATPase-overexpressing cells determine the distribution of malaria parasite oocysts on the midguts of mosquitoes. The Journal of Biological Chemistry 274, 12650–12655.CrossRefGoogle Scholar
DAVIES, E. E. ( 1974). Ultrastructural studies on the early ookinete stage of Plasmodium berghei nigeriensis and its transformation into an oocyst. Annals of Tropical Medicine and Parasitology 68, 283–290.CrossRefGoogle Scholar
FREYVOGEL, T. A. & STÄUBLI, W. ( 1965). The formation of the peritrophic membrane in Culicidae. Acta Tropica 22, 118–147.Google Scholar
GARNHAM, P. C. C., BIRD, R. G. & BAKER, J. R. ( 1962). Electron microscope studies of motile stages of malaria parasites. III. The ookinetes of Haemamoeba and Plasmodium. Transactions of the Royal Society of Tropical Medicine and Hygiene 56, 116–120.CrossRefGoogle Scholar
GARNHAM, P. C. C., BIRD, R. G., BAKER, J. R., DESSER, S. S. & EL NAHAL, H. M. ( 1969). Electron microscope studies on motile stages of malaria parasites. VI. The ookinete of Plasmodium berghei yoelii and its transformation into the early oocyst. Transactions of the Royal Society of Tropical Medicine and Hygiene 63, 187–194.Google Scholar
GLÄTTLI, E., RUDIN, W. & HECKER, H. ( 1987). Immunoelectron microscopic demonstration of pancreatic polypeptide in midgut epithelium of hematophagous dipterans. Journal of Histochemistry and Cytochemistry 35, 891–896.CrossRefGoogle Scholar
HAN, Y. S. & BARILLAS-MURY, C. ( 2002). Implications of Time Bomb model of ookinete invasion of midgut cells. Insect Biochemistry and Molecular Biology 32, 1311–1316.CrossRefGoogle Scholar
HAN, Y. S., THOMPSON, J., KAFATOS, F. C. & BARILLAS-MURY, C. ( 2000). Molecular interactions between Anopheles stephensi midgut cells and Plasmodium berghei: the time bomb theory of ookinete invasion of mosquitoes. The European Molecular Biology Organisation Journal 19, 6030–6040.CrossRefGoogle Scholar
HECKER, H. ( 1977). Structure and function of midgut epithelial cells in Culicidae mosquitoes (Insecta, Diptera). Cell and Tissue Research 184, 321–341.CrossRefGoogle Scholar
HOUK, E. J. ( 1977). Midgut ultrastructure of Culex tarsalis (Diptera: Culcidae) before and after a bloodmeal. Tissue and Cell 9, 103–118.CrossRefGoogle Scholar
HOUK, E. J., KRAMER, L. D., HARDY, J. L. & CHILES, R. E. ( 1985). Western equine encephalomyelitis virus: in vivo infection and morphogenesis in mosquito mesenteronal epithelial cells. Virus Research 2, 123–138.CrossRefGoogle Scholar
HUFF, C. G. ( 1934). Comparative studies on susceptible and insusceptible Culex pipiens in relation to infections with Plasmodium cathemerium and P. relictum. American Journal of Hygiene 19, 123–147.CrossRefGoogle Scholar
IFEDIBA, T. & VANDERBERG, J. P. ( 1981). Complete in vitro maturation of Plasmodium falciparum gametocytes. Nature, London 294, 364–366.CrossRefGoogle Scholar
INDACOCHEA, A. A. ( 1935). La penetración del oökineto del Plasmodium falciparum en el epitelio intestinal del Anopheles maculipennis. Rivista di Malariologia 14, 117–120.Google Scholar
MAIER, W. A. ( 1973). Über die Mortalität von Culex pipiens fatigans nach Infektion mit Plasmodium cathemerium. Zeitschrift für Parasitkunde 41, 11–28.Google Scholar
MAIER, W. A. ( 1987). Letter. Interaction of malaria with mosquitoes. Reply. Parasitology Today 3, 369–370.Google Scholar
MAIER, W. A., BECKER-FELDMAN, H. & SEITZ, H. M. ( 1987). Pathology of malaria-infected mosquitoes. Parasitology Today 3, 216–218.CrossRefGoogle Scholar
MEHLHORN, H. & PETERS, W. ( 1980). The formation of kinetes and oocyst in Plasmodium gallinaceum (Haemosporidia) and considerations on phylogenetic relationships between Haemosporidia, Piroplasmida and other Coccidia. Protistologica 16, 135–154.Google Scholar
MEIS, J. F. G. M. & PONNUDURAI, T. ( 1987 a). Ultrastructural studies on the interaction of Plasmodium falciparum ookinetes with the midgut epithelium of Anopheles stephensi mosquitoes. Parasitology Research 73, 500–506.Google Scholar
MEIS, J. F. G. M. & PONNUDURAI, T. ( 1987 b). Letter. Interaction of malaria with mosquitoes. Parasitology Today 3, 369.Google Scholar
MEIS, J. F. G. M., POOL, G., VAN GEMERT, G. J., LENSEN, A. H., PONNUDURAI, T. & MEUWISSEN, J. H. ( 1989). Plasmodium falciparum ookinetes migrate intercellularly through Anopheles stephensi midgut epithelium. Parasitology Research 76, 13–19.CrossRefGoogle Scholar
OKUDA, K., CAROCI, A., RIBOLLA, P., DE BIANCHI, A. & BIJOVSKY, A. ( 2002). Functional morphology of adult female Culex quinquefasciatus midgut during blood digestion. Tissue and Cell 34, 210–219.CrossRefGoogle Scholar
OMAR, M. S. ( 1968). Vergleichende Beobachtungen über die Entwicklung von Plasmodium cynomolgi bastianellii in Anopheles stephensi und Anopheles albimanus. Zeitschrift für Tropenmedizin und Parasitologie 19, 370–389.Google Scholar
PASKEWITZ, S. M., BROWN, M. R., LEA, A. O. & COLLINS, F. H. ( 1988). Ultrastructure of the encapsulation of Plasmodium cynomolgi (B strain) on the midgut of a refractory strain of Anopheles gambiae. Journal of Parasitology 74, 432–439.CrossRefGoogle Scholar
PONNUDURAI, T., MEUWISSEN, J. H., LEEUWENBERG, A. D., VERHAVE, J. P. & LENSEN, A. H. ( 1982). The production of mature gametocytes of Plasmodium falciparum in continuous cultures of different isolates infective to mosquitoes. Transactions of the Royal Society of Tropical Medicine and Hygiene 76, 242–250.CrossRefGoogle Scholar
REICHENOW, E. ( 1932). Die Entwicklung von Proteosoma circumflexum in Theobaldia annulata nebst Beobachtungen über das Verhalten anderer Vogelplasmodien in Mücken. Jenaische Zeitschrift für Medizin und Naturwissenschaft 67, 443–451.Google Scholar
SHAHABUDDIN, M. ( 2002). Do Plasmodium ookinetes invade a specific cell type in the mosquito midgut? Trends in Parasitology 18, 157–161.Google Scholar
SHAHABUDDIN, M. & PIMENTA, P. F. ( 1998). Plasmodium gallinaceum preferentially invades vesicular ATPase-expressing cells in Aedes aegypti midgut. Proceedings of the National Academy of Sciences, USA 95, 3385–3389.CrossRefGoogle Scholar
SINDEN, R. E. & BILLINGSLEY, P. F. ( 2001). Plasmodium invasion of mosquito cells: hawk or dove? Trends in Parasitology 17, 209–212.Google Scholar
SOKAL, R. R. & ROHLF, F. J. ( 1995). Biometry, 3rd Edn. W. H. Freeman & Company, New York.
STOHLER, H. ( 1957). Analyse des Infektionsverlaufes von Plasmodium gallinaceum im Darme von Aedes aegypti. Acta Tropica 14, 302–352.Google Scholar
SYAFRUDDIN ARAKAWA, R., KAMIMURA, K. & KAWAMOTO, F. ( 1991). Penetration of the mosquito midgut wall by the ookinetes of Plasmodium yoelii nigeriensis. Parasitology Research 77, 230–236.CrossRefGoogle Scholar
TORII, M., NAKAMURA, K., SIEBER, K. P., MILLER, L. H. & AIKAWA, M. ( 1992). Penetration of the mosquito (Aedes aegypti) midgut wall by the ookinetes of Plasmodium gallinaceum. Journal of Protozoology 39, 449–454.CrossRefGoogle Scholar
VERNICK, K. D., FUJIOKA, H. & AIKAWA, M. ( 1999). Plasmodium gallinaceum: a novel morphology of malaria ookinetes in the midgut of the mosquito vector. Experimental Parasitology 91, 362–366.CrossRefGoogle Scholar
WEAVER, S. C., LORENZ, L. H. & SCOTT, T. W. ( 1992). Pathologic changes in the midgut of Culex tarsalis following infection with Western equine encephalomyelitis virus. American Journal of Tropical Medicine and Hygiene 47, 691–701.CrossRefGoogle Scholar
WEAVER, S. C. & SCOTT, T. W. ( 1990 a). Peritrophic membrane formation and cellular turnover in the midgut of Culiseta melanura (Diptera: Culicidae). Journal of Medical Entomology 27, 864–873.Google Scholar
WEAVER, S. C. & SCOTT, T. W. ( 1990 b). Ultrastructural changes in the abdominal midgut of the mosquito, Culiseta melanura, during the gonotrophic cycle. Tissue and Cell 22, 895–909.Google Scholar
WEAVER, S. C., SCOTT, T. W., LORENZ, L. H., LERDTHUSNEE, K. & ROMOSER, W. S. ( 1988). Togavirus-associated pathologic changes in the midgut of a natural mosquito vector. Journal of Virology 62, 2083–2090.Google Scholar
ZAR, J. H. ( 1984). Biostatistical Analysis, 3rd Edn. Prentice-Hall, Englewood Cliffs, New Jersey.
ZIELER, H. & DVORAK, J. A. ( 2000). Invasion in vitro of mosquito midgut cells by the malaria parasite proceeds by a conserved mechanism and results in death of the invaded midgut cells. Proceedings of the National Academy of Sciences, USA 97, 11516–11521.CrossRefGoogle Scholar