Inbred strains derived from feral mice reveal new pathogenic mechanisms of experimental leishmaniasis due to Leishmania major.
Two inbred mouse strains, derived from feral founders, are susceptible to experimental leishmaniasis due to Leishmania major and support a disease of a severity intermediate between those observed in strains C57BL/6 and BALB/c. Mice of the MAI strain develop a severe, nonhealing, but nonfatal disease with no resistance to a secondary parasite challenge. The immunological responses showed a TH2 dominance characterized by an early peak of interleukin-4 (IL-4) and IL-13. However, neutralization of IL-4, which leads to a resistance phenotype in BALB/c mice, has no effect on disease progression in MAI mice. Mice of strain PWK develop a protracted but self-healing disease, characterized by a mixed TH1-plus-TH2 pattern of immune responses in which IL-10 plays an aggravating role, and acquire resistance to a secondary challenge. These features are close to those observed in human cutaneous leishmaniasis due to L. major and make PWK mice a suitable model for the human disease.
Laboratory of Immunology (LAF 301), Institut Pasteur de Tunis, WHO Collaborating Center for Training and Research on Leishmaniasis, 1002 Tunis-Belvedere, Tunisia.
Besma E C
BE
Babay
Hechmi
H
Louzir
Chahnaz
C
Kebaïer
Samir
S
Boubaker
Koussay
K
Dellagi
Pierre-André
PA
Cazenave
D000818:Animals; D000835:Animals, Wild / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D018320:Leishmania major / Q000472:pathogenicity*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology* / Q000469:parasitology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000235:genetics; D008810:Mice, Inbred C57BL / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines