title: Innate refractoriness of the Lewis rat to toxoplasmosis is a dominant trait that is intrinsic to bone marrow-derived cells.
abstract: 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 F(1) 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.
authors.affiliation: CNRS UMR 5163, Institut Jean Roget, Université Joseph Fourier, UFR de Biologie, Grenoble, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Sergent
authors.forename: Bastien
authors.initials: B
authors.lastname: Cautain
authors.forename: Jamal
authors.initials: J
authors.lastname: Khalife
authors.forename: Didier
authors.initials: D
authors.lastname: Deslée
authors.forename: Patrick
authors.initials: P
authors.lastname: Bastien
authors.forename: Anne
authors.initials: A
authors.lastname: Dao
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dubremetz
authors.forename: Gilbert J
authors.initials: GJ
authors.lastname: Fournié
authors.forename: Abdelhadi
authors.initials: A
authors.lastname: Saoudi
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Cesbron-Delauw
mesh_terms: D000818:Animals; D001921:Brain / Q000469:parasitology; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000378:metabolism; D006649:Histocompatibility Antigens / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics*; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D007422:Intestines / Q000469:parasitology; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew / Q000235:genetics* / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000235:genetics* / Q000276:immunology*
chemical_list: D006649:Histocompatibility Antigens; D007074:Immunoglobulin G; D007371:Interferon-gamma