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Infection and Immunity, October 2005, p. 6990-6997, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6990-6997.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Innate Refractoriness of the Lewis Rat to Toxoplasmosis Is a Dominant Trait That Is Intrinsic to Bone Marrow-Derived Cells

Véronique Sergent,1,4 Bastien Cautain,2 Jamal Khalife,3 Didier Deslée,4 Patrick Bastien,5 Anne Dao,6 Jean-François Dubremetz,4,7 Gilbert J. Fournié,2 Abdelhadi Saoudi,2,{dagger} and Marie-France Cesbron-Delauw1*,{dagger}

CNRS UMR 5163, Institut Jean Roget, Université Joseph Fourier, UFR de Biologie, Grenoble, France,1 INSERM U563, CPTP, IFR 30 CHU Purpan, 31059 Toulouse, France,2 INSERM U547, Institut Pasteur de Lille, Lille, France,3 Institut de Biologie de Lille, Lille, France,4 CNRS UMR 5093, Université de Montpellier 1, Montpellier, France,5 Parasitologie, CHU Brabois, Nancy, France,6 CNRS UMR 5539, Université de Montpellier 2, Montpellier, France7

Received 16 December 2004/ Returned for modification 21 January 2005/ Accepted 27 May 2005

Toxoplasmosis is a ubiquitous parasitic infection causing a wide spectrum of diseases. It is usually asymptomatic but can lead to severe ocular and neurological disorders. Among the small-animal models available to study factors that determine susceptibility to toxoplasmosis, the rat appears to be rather similar to humans, particularly in terms of resistance to acute infection. Here, we demonstrate that the Lewis (LEW) rat strain displays an unexpected refractoriness to Toxoplasma infection. Complete resistance was assessed by both negative anti-Toxoplasma serology and lack of detection of the parasite during the course of infection. In this model, sex, age, major histocompatibility complex, and inoculum size had no effect on resistance. Interestingly, progeny from F1 hybrid crosses between Fischer (F344) or Brown Norway susceptible rats and LEW resistant rats were also fully resistant, showing a dominant effect of the gene or set of genes. Furthermore, resistance of the LEW rat was shown to be dependent on hematopoietic cells and partially abrogated by neutralization of endogenous gamma interferon. To our knowledge, this is the first observation of a rodent strain that is refractory to Toxoplasma infection. This model is therefore an attractive and powerful tool to dissect host genetic factors involved in susceptibility to toxoplasmosis.

* Corresponding author. Mailing address: LAPM, UMR 5163 CNRS-UJF, Institut Jean Roget, Campus Santé, Domaine de La Merci, 38700 La Tronche, France. Phone: 33 4 76 63 74 63. Fax: 33 4 76 63 74 97. E-mail: marie-france.cesbron{at}ujf-grenoble.fr.

Editor: J. F. Urban, Jr.

{dagger} M.-F.C.-D. and A.S. codirected this work.

Infection and Immunity, October 2005, p. 6990-6997, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6990-6997.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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