Differential effects of interferon-gamma and tumor necrosis factor-alpha on Toxoplasma gondii proliferation in organotypic rat brain slice cultures.

Scheidegger, Alexandra; Vonlaufen, Nathalie Françoise F.; Naguleswaran, Arunasalam; Gianinazzi, Christian; Müller, Norbert; Leib, Stephen; Hemphill, Andrew (2005). Differential effects of interferon-gamma and tumor necrosis factor-alpha on Toxoplasma gondii proliferation in organotypic rat brain slice cultures. Journal of parasitology, 91(2), pp. 307-315. American Society of Parasitologists 10.1645/GE-379R

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Organotypic slice culture explants of rat cortical tissue infected with Toxoplasma gondii tachyzoites were applied as an in vitro model to investigate host-pathogen interactions in cerebral toxoplasmosis. The kinetics of parasite proliferation and the effects of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in infected organotypic cultures were monitored by light microscopy, transmission electron microscopy (TEM), and quantitative polymerase chain reaction (PCR) assay. As assessed by the loss of the structural integrity of the glial fibrillary acidic protein-intermediate filament network, tachyzoites infected and proliferated mainly within astrocytes, whereas neurons and microglia remained largely unaffected. Toxoplasma gondii proliferation was severely inhibited by IFN-y. However, this inhibition was not linked to tachyzoite-to-bradyzoite stage conversion. In contrast, TNF-alpha treatment resulted in a dramatically enhanced proliferation rate of the parasite. The cellular integrity in IFN-gamma-treated organotypic slice cultures was severely impaired compared with untreated and TNF-alpha-treated cultures. Thus, on infection of organotypic neuronal cultures, IFN-gamma and TNF-alpha exhibit largely detrimental effects, which could contribute to either inhibition or acceleration of parasite proliferation during cerebral toxoplasmosis.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

UniBE Contributor:

Vonlaufen, Nathalie Françoise F.; Naguleswaran, Arunasalam; Gianinazzi, Christian; Müller, Norbert; Leib, Stephen and Hemphill, Andrew

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0022-3395

Publisher:

American Society of Parasitologists

Language:

English

Submitter:

Stephen Leib

Date Deposited:

25 Aug 2014 16:50

Last Modified:

19 Jul 2018 15:54

Publisher DOI:

10.1645/GE-379R

PubMed ID:

15986605

URI:

https://boris.unibe.ch/id/eprint/52732

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