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The liver stage of Plasmodium berghei inhibits host cell apoptosis

Van De Sand, Claudia; Horstmann, Sebastian; Schmidt, Anja LU ; Sturm, Angelika; Bolte, Stefanie; Krueger, Andreas; Lütgehetmann, Marc; Pollok, Jörg Matthias; Libert, Claude and Heussler, Volker T. (2005) In Molecular Microbiology 58(3). p.731-742
Abstract

Plasmodium berghei is the causative agent of rodent malaria and is widely used as a model system to study the liver stage of Plasmodium parasites. The entry of P. berghei sporozoites into hepatocytes has extensively been studied, but little is known about parasite-host interaction during later developmental stages of the intracellular parasite. Growth of the parasite far beyond the normal size of the host cell is an important stress factor for the infected cell. Cell stress is known to trigger programmed cell death (apoptosis) and we examined several apoptotic markers in P. berghei-infected cells and compared their level of expression and their distribution to that of non-infected cells. As none of the apoptotic markers investigated... (More)

Plasmodium berghei is the causative agent of rodent malaria and is widely used as a model system to study the liver stage of Plasmodium parasites. The entry of P. berghei sporozoites into hepatocytes has extensively been studied, but little is known about parasite-host interaction during later developmental stages of the intracellular parasite. Growth of the parasite far beyond the normal size of the host cell is an important stress factor for the infected cell. Cell stress is known to trigger programmed cell death (apoptosis) and we examined several apoptotic markers in P. berghei-infected cells and compared their level of expression and their distribution to that of non-infected cells. As none of the apoptotic markers investigated were found altered in infected cells, we hypothesized that parasite infection might confer resistance to apoptosis of the host cell. Treatment with peroxide or serum deprivation induced apoptosis in non-infected HepG2 cells, whereas P. berghei-infected cells appeared protected, indicating that the parasite interferes indeed with the apoptotic machinery of the host cell. To prove the physiological relevance of these results, mice were infected with high numbers of P. berghei sporozoites and treated with tumour necrosis factor (TNF)-α/D-galactosamine to induce massive liver apoptosis. Liver sections of these mice, stained for degraded DNA, confirmed that infected cells containing viable parasites were protected from programmed cell death. However, in non-treated control mice as well as in TNF-α-treated mice a small proportion of dead intracellular parasites with degraded DNA were detected. Most hepatocytes containing dead parasites provoked an infiltration of immunocompetent cells, indicating that these cells are no longer protected from cell death.

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author
publishing date
type
Contribution to journal
publication status
published
in
Molecular Microbiology
volume
58
issue
3
pages
12 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:27444440200
ISSN
0950-382X
DOI
10.1111/j.1365-2958.2005.04888.x
language
English
LU publication?
no
id
528b2493-5236-4179-9f21-27ea32ab3af6
date added to LUP
2017-06-10 23:38:04
date last changed
2017-09-24 05:11:32
@article{528b2493-5236-4179-9f21-27ea32ab3af6,
  abstract     = {<p>Plasmodium berghei is the causative agent of rodent malaria and is widely used as a model system to study the liver stage of Plasmodium parasites. The entry of P. berghei sporozoites into hepatocytes has extensively been studied, but little is known about parasite-host interaction during later developmental stages of the intracellular parasite. Growth of the parasite far beyond the normal size of the host cell is an important stress factor for the infected cell. Cell stress is known to trigger programmed cell death (apoptosis) and we examined several apoptotic markers in P. berghei-infected cells and compared their level of expression and their distribution to that of non-infected cells. As none of the apoptotic markers investigated were found altered in infected cells, we hypothesized that parasite infection might confer resistance to apoptosis of the host cell. Treatment with peroxide or serum deprivation induced apoptosis in non-infected HepG2 cells, whereas P. berghei-infected cells appeared protected, indicating that the parasite interferes indeed with the apoptotic machinery of the host cell. To prove the physiological relevance of these results, mice were infected with high numbers of P. berghei sporozoites and treated with tumour necrosis factor (TNF)-α/D-galactosamine to induce massive liver apoptosis. Liver sections of these mice, stained for degraded DNA, confirmed that infected cells containing viable parasites were protected from programmed cell death. However, in non-treated control mice as well as in TNF-α-treated mice a small proportion of dead intracellular parasites with degraded DNA were detected. Most hepatocytes containing dead parasites provoked an infiltration of immunocompetent cells, indicating that these cells are no longer protected from cell death.</p>},
  author       = {Van De Sand, Claudia and Horstmann, Sebastian and Schmidt, Anja and Sturm, Angelika and Bolte, Stefanie and Krueger, Andreas and Lütgehetmann, Marc and Pollok, Jörg Matthias and Libert, Claude and Heussler, Volker T.},
  issn         = {0950-382X},
  language     = {eng},
  number       = {3},
  pages        = {731--742},
  publisher    = {Wiley-Blackwell},
  series       = {Molecular Microbiology},
  title        = {The liver stage of Plasmodium berghei inhibits host cell apoptosis},
  url          = {http://dx.doi.org/10.1111/j.1365-2958.2005.04888.x},
  volume       = {58},
  year         = {2005},
}