The rat Toxo1 locus directs toxoplasmosis outcome and controls parasite proliferation and spreading by macrophage-dependent mechanisms. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2006

The rat Toxo1 locus directs toxoplasmosis outcome and controls parasite proliferation and spreading by macrophage-dependent mechanisms.

Pierre Cavaillès
  • Fonction : Auteur
Véronique Sergent
  • Fonction : Auteur
Cordelia Bisanz
  • Fonction : Auteur
Olivier Papapietro
  • Fonction : Auteur
Céline Colacios
Magali Mas
  • Fonction : Auteur
  • PersonId : 756165
  • IdRef : 177853069
Jean-François Subra
  • Fonction : Auteur
Dominique Lagrange
  • Fonction : Auteur
Maryline Calise
  • Fonction : Auteur
Sylvie Appolinaire
  • Fonction : Auteur
Thomas Faraut
Philippe Druet
  • Fonction : Auteur
Abdelhadi Saoudi
Marie-Hélène Bessieres
  • Fonction : Auteur
Bernard Pipy
Marie-France Cesbron-Delauw
Gilbert J Fournié
  • Fonction : Auteur

Résumé

Toxoplasmosis is a healthcare problem in pregnant women and immunocompromised patients. Like humans, rats usually develop a subclinical chronic infection. LEW rats exhibit total resistance to Toxoplasma gondii infection, which is expressed in a dominant mode. A genome-wide search carried out in a cohort of F(2) progeny of susceptible BN and resistant LEW rats led to identify on chromosome 10 a major locus of control, which we called Toxo1. Using reciprocal BN and LEW lines congenic for chromosome 10 genomic regions from the other strain, Toxo1 was found to govern the issue of T. gondii infection whatever the remaining genome. Analyzes of rats characterized by genomic recombination within Toxo1, reduced the interval down to a 1.7-cM region syntenic to human 17p13. In vitro studies showed that the Toxo1-mediated refractoriness to T. gondii infection is associated with the ability of the macrophage to impede the proliferation of the parasite within the parasitophorous vacuole. In contrast, proliferation was observed in fibroblasts whatever the genomic origin of Toxo1. Furthermore, ex vivo studies indicate that macrophage controls parasitic infection spreading by a Toxo1-mediated mechanism. This forward genetics approach should ultimately unravel a major pathway of innate resistance to toxoplasmosis and possibly to other apicomplexan parasitic diseases.

Dates et versions

hal-00171244 , version 1 (12-09-2007)

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Citer

Pierre Cavaillès, Véronique Sergent, Cordelia Bisanz, Olivier Papapietro, Céline Colacios, et al.. The rat Toxo1 locus directs toxoplasmosis outcome and controls parasite proliferation and spreading by macrophage-dependent mechanisms.. Proceedings of the National Academy of Sciences of the United States of America, 2006, 103 (3), pp.744-9. ⟨10.1073/pnas.0506643103⟩. ⟨hal-00171244⟩
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