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Infection and Immunity, August 2008, p. 3491-3501, Vol. 76, No. 8
0019-9567/08/$08.00+0     doi:10.1128/IAI.00254-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Temporal and Spatial Distribution of Toxoplasma gondii Differentiation into Bradyzoites and Tissue Cyst Formation In Vivo{triangledown}

Manlio Di Cristina,1 Daniela Marocco,1 Roberto Galizi,1 Carla Proietti,1 Roberta Spaccapelo,1 and Andrea Crisanti1,2*

Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via Del Giochetto, 06122 Perugia, Italy,1 Division of Molecular and Cell Biology, Imperial College, Imperial College Road, London SW7 2AZ, United Kingdom2

Received 22 February 2008/ Returned for modification 31 March 2008/ Accepted 15 May 2008

During Toxoplasma gondii infection, a fraction of the multiplying parasites, the tachyzoites, converts into bradyzoites, a dormant stage, which form tissue cysts localized mainly in brain, heart, and skeletal muscles that persist for several years after infection. At this stage the parasite is protected from the immune system, and it is believed to be inaccessible to drugs. While the long persistence of tissue cysts does not represent a medical problem for healthy individuals, this condition represents a major risk for patients with a compromised immune system, who can develop recrudescent life-threatening T. gondii infections. We have investigated for the first time the dynamics and the kinetics of tachyzoite-to-bradyzoite interconversion and cyst formation in vivo by using stage-specific bioluminescent parasites in a mouse model. Our findings provide a new framework for understanding the process of bradyzoite differentiation in vivo. We have also demonstrated that complex molecules such as D-luciferin have access to tissue cysts and are metabolically processed, thus providing a rationale for developing drugs that attack the parasite at this developmental stage.

* Corresponding author. Mailing address: Division of Molecular and Cell Biology, Imperial College, Imperial College Road, London SW7 2AZ, United Kingdom. Phone: 44 207 5945426. Fax: 44 207 5945439. E-mail: acrs{at}imperial.ac.uk

{triangledown} Published ahead of print on 27 May 2008.

Editor: W. A. Petri, Jr.

Infection and Immunity, August 2008, p. 3491-3501, Vol. 76, No. 8
0019-9567/08/$08.00+0     doi:10.1128/IAI.00254-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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