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Aerosols transmit prions to immunocompetent and immunodeficient mice.

Haybaeck J, Heikenwalder M, Klevenz B, Schwarz P, Margalith I, Bridel C, Mertz K, Zirdum E, Petsch B, Fuchs TJ, Stitz L, Aguzzi A - PLoS Pathog. (2011)

Bottom Line: However, prions are not generally considered to be airborne.We conclude that aerogenic exposure to prions is very efficacious and can lead to direct invasion of neural pathways without an obligatory replicative phase in lymphoid organs.This previously unappreciated risk for airborne prion transmission may warrant re-thinking on prion biosafety guidelines in research and diagnostic laboratories.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.

ABSTRACT
Prions, the agents causing transmissible spongiform encephalopathies, colonize the brain of hosts after oral, parenteral, intralingual, or even transdermal uptake. However, prions are not generally considered to be airborne. Here we report that inbred and crossbred wild-type mice, as well as tga20 transgenic mice overexpressing PrP(C), efficiently develop scrapie upon exposure to aerosolized prions. NSE-PrP transgenic mice, which express PrP(C) selectively in neurons, were also susceptible to airborne prions. Aerogenic infection occurred also in mice lacking B- and T-lymphocytes, NK-cells, follicular dendritic cells or complement components. Brains of diseased mice contained PrP(Sc) and transmitted scrapie when inoculated into further mice. We conclude that aerogenic exposure to prions is very efficacious and can lead to direct invasion of neural pathways without an obligatory replicative phase in lymphoid organs. This previously unappreciated risk for airborne prion transmission may warrant re-thinking on prion biosafety guidelines in research and diagnostic laboratories.

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Prion transmission through aerosols in immunocompromised mice.Survival curves, lesion severity score analysis (radar plots), and representative histopathological micrographs of mice with genetically or pharmacologically impaired components of the immune system (JH−/−, γCRag2−/−A),129Sv mice treated with LTβR-Ig or with muIgG (B), and LTβR−/−, and CD40−/− mice (C). All mice were exposed for 10 min to aerosolized 20% IBH. Stain code: HE (spongiosis, gliosis, neuronal cell loss), SAF84 (PrPSc deposits), GFAP (astrogliosis) and Iba-1 (microglial activation) as in Fig. 1H. Scale bars: 100µm.
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ppat-1001257-g003: Prion transmission through aerosols in immunocompromised mice.Survival curves, lesion severity score analysis (radar plots), and representative histopathological micrographs of mice with genetically or pharmacologically impaired components of the immune system (JH−/−, γCRag2−/−A),129Sv mice treated with LTβR-Ig or with muIgG (B), and LTβR−/−, and CD40−/− mice (C). All mice were exposed for 10 min to aerosolized 20% IBH. Stain code: HE (spongiosis, gliosis, neuronal cell loss), SAF84 (PrPSc deposits), GFAP (astrogliosis) and Iba-1 (microglial activation) as in Fig. 1H. Scale bars: 100µm.

Mentions: In many paradigms of extracerebral prion infection, efficient neuroinvasion relies on the anatomical and physiological integrity of several immune system components [40], [42], [43], [44]. To determine whether this is true for aerosolic prion challenges, we exposed immunodeficient mouse strains to prion aerosols. This series of experiments included JH−/− mice, which selectively lack B-cells, and γCRag2−/− mice which are devoid of mature B-, T- and NK-cells (Fig. 3A). Upon exposure to prion aerosoIs (20% IBH; exposure time 10 min) both JH−/− and γCRag2−/− mice succumbed to scrapie with a 100% attack rate (JH−/−: n = 6, 181±21 dpi; γCRag2−/−: n = 11, 185±41 dpi, p = 0.65). The incubation times were not significantly different to those of C57BL/6 wt mice exposed to prion aerosols (JH−/− mice: p = 0.9; γCRag2−/− mice: p = 0.7).


Aerosols transmit prions to immunocompetent and immunodeficient mice.

Haybaeck J, Heikenwalder M, Klevenz B, Schwarz P, Margalith I, Bridel C, Mertz K, Zirdum E, Petsch B, Fuchs TJ, Stitz L, Aguzzi A - PLoS Pathog. (2011)

Prion transmission through aerosols in immunocompromised mice.Survival curves, lesion severity score analysis (radar plots), and representative histopathological micrographs of mice with genetically or pharmacologically impaired components of the immune system (JH−/−, γCRag2−/−A),129Sv mice treated with LTβR-Ig or with muIgG (B), and LTβR−/−, and CD40−/− mice (C). All mice were exposed for 10 min to aerosolized 20% IBH. Stain code: HE (spongiosis, gliosis, neuronal cell loss), SAF84 (PrPSc deposits), GFAP (astrogliosis) and Iba-1 (microglial activation) as in Fig. 1H. Scale bars: 100µm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3020930&req=5

ppat-1001257-g003: Prion transmission through aerosols in immunocompromised mice.Survival curves, lesion severity score analysis (radar plots), and representative histopathological micrographs of mice with genetically or pharmacologically impaired components of the immune system (JH−/−, γCRag2−/−A),129Sv mice treated with LTβR-Ig or with muIgG (B), and LTβR−/−, and CD40−/− mice (C). All mice were exposed for 10 min to aerosolized 20% IBH. Stain code: HE (spongiosis, gliosis, neuronal cell loss), SAF84 (PrPSc deposits), GFAP (astrogliosis) and Iba-1 (microglial activation) as in Fig. 1H. Scale bars: 100µm.
Mentions: In many paradigms of extracerebral prion infection, efficient neuroinvasion relies on the anatomical and physiological integrity of several immune system components [40], [42], [43], [44]. To determine whether this is true for aerosolic prion challenges, we exposed immunodeficient mouse strains to prion aerosols. This series of experiments included JH−/− mice, which selectively lack B-cells, and γCRag2−/− mice which are devoid of mature B-, T- and NK-cells (Fig. 3A). Upon exposure to prion aerosoIs (20% IBH; exposure time 10 min) both JH−/− and γCRag2−/− mice succumbed to scrapie with a 100% attack rate (JH−/−: n = 6, 181±21 dpi; γCRag2−/−: n = 11, 185±41 dpi, p = 0.65). The incubation times were not significantly different to those of C57BL/6 wt mice exposed to prion aerosols (JH−/− mice: p = 0.9; γCRag2−/− mice: p = 0.7).

Bottom Line: However, prions are not generally considered to be airborne.We conclude that aerogenic exposure to prions is very efficacious and can lead to direct invasion of neural pathways without an obligatory replicative phase in lymphoid organs.This previously unappreciated risk for airborne prion transmission may warrant re-thinking on prion biosafety guidelines in research and diagnostic laboratories.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.

ABSTRACT
Prions, the agents causing transmissible spongiform encephalopathies, colonize the brain of hosts after oral, parenteral, intralingual, or even transdermal uptake. However, prions are not generally considered to be airborne. Here we report that inbred and crossbred wild-type mice, as well as tga20 transgenic mice overexpressing PrP(C), efficiently develop scrapie upon exposure to aerosolized prions. NSE-PrP transgenic mice, which express PrP(C) selectively in neurons, were also susceptible to airborne prions. Aerogenic infection occurred also in mice lacking B- and T-lymphocytes, NK-cells, follicular dendritic cells or complement components. Brains of diseased mice contained PrP(Sc) and transmitted scrapie when inoculated into further mice. We conclude that aerogenic exposure to prions is very efficacious and can lead to direct invasion of neural pathways without an obligatory replicative phase in lymphoid organs. This previously unappreciated risk for airborne prion transmission may warrant re-thinking on prion biosafety guidelines in research and diagnostic laboratories.

Show MeSH
Related in: MedlinePlus