title: Experimental tuberculosis in the Wistar rat: a model for protective immunity and control of infection.
abstract: BACKGROUND
  Despite the availability of many animal models for tuberculosis (TB) research, there still exists a need for better understanding of the quiescent stage of disease observed in many humans. Here, we explored the use of the Wistar rat model for the study of protective immunity and control of Mycobacterium tuberculosis (Mtb) infection.
  
  
  RESULTS
  The kinetics of bacillary growth, evaluated by the colony stimulating assay (CFU) and the extent of lung pathology in Mtb infected Wistar rats were dependent on the virulence of the strains and the size of the infecting inoculums. Bacillary growth control was associated with induction of T helper type 1 (Th1) activation, the magnitude of which was also Mtb strain and dose dependent. Histopathology analysis of the infected lungs demonstrated the formation of well organized granulomas comprising epithelioid cells, multinucleated giant cells and foamy macrophages surrounded by large numbers of lymphocytes. The late stage subclinical form of disease was reactivated by immunosuppression leading to increased lung CFU.
  
  
  CONCLUSIONS
  The Wistar rat is a valuable model for better understanding host-pathogen interactions that result in control of Mtb infection and potentially establishment of latent TB. These properties together with the ease of manipulation, relatively low cost and well established use of rats in toxicology and pharmacokinetic analyses make the rat a good animal model for TB drug discovery.
authors.affiliation: Novartis Institute for Tropical Diseases, Singapore, Singapore.
authors.forename: Amit
authors.initials: A
authors.lastname: Singhal
authors.forename: El Moukhtar
authors.initials: el M
authors.lastname: Aliouat
authors.forename: Maxime
authors.initials: M
authors.lastname: Hervé
authors.forename: Vanessa
authors.initials: V
authors.lastname: Mathys
authors.forename: Mehdi
authors.initials: M
authors.lastname: Kiass
authors.forename: Colette
authors.initials: C
authors.lastname: Creusy
authors.forename: Baptiste
authors.initials: B
authors.lastname: Delaire
authors.forename: Liana
authors.initials: L
authors.lastname: Tsenova
authors.forename: Laurence
authors.initials: L
authors.lastname: Fleurisse
authors.forename: Julie
authors.initials: J
authors.lastname: Bertout
authors.forename: Luis
authors.initials: L
authors.lastname: Camacho
authors.forename: Damian
authors.initials: D
authors.lastname: Foo
authors.forename: Hui Chien
authors.initials: HC
authors.lastname: Tay
authors.forename: Jie Yee
authors.initials: JY
authors.lastname: Siew
authors.forename: Warda
authors.initials: W
authors.lastname: Boukhouchi
authors.forename: Marta
authors.initials: M
authors.lastname: Romano
authors.forename: Barun
authors.initials: B
authors.lastname: Mathema
authors.forename: Véronique
authors.initials: V
authors.lastname: Dartois
authors.forename: Gilla
authors.initials: G
authors.lastname: Kaplan
authors.forename: Pablo
authors.initials: P
authors.lastname: Bifani
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D051381:Rats; D017208:Rats, Wistar; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control