title: Leishmaniasis host response loci (lmr1-3) modify disease severity through a Th1/Th2-independent pathway.
abstract: The severity of disease caused by infection with Leishmania major depends critically on the genetics of the host. Early induction of T helper (Th)1-type immune responses in the resistant C57BL/6 mice and Th2-type responses in the susceptible BALB/c mice are thought to determine cure or disease, respectively. We have previously mapped three host response loci in a genetic cross between C57BL/6 and BALB/c mice, and here we show definitively the involvement of these loci in disease severity using animals congenic for each of the loci. Surprisingly, in the late stage of infection when the difference in disease severity between congenic and parental mice was most pronounced, their cytokine profile correlated with the genetic background of the mice and not with the severity of disease. This indicates that the loci that we have mapped are acting by a mechanism independent of Th phenotype.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia.
authors.forename: C M
authors.initials: CM
authors.lastname: Elso
authors.forename: L J
authors.initials: LJ
authors.lastname: Roberts
authors.forename: G K
authors.initials: GK
authors.lastname: Smyth
authors.forename: R J
authors.initials: RJ
authors.lastname: Thomson
authors.forename: T M
authors.initials: TM
authors.lastname: Baldwin
authors.forename: S J
authors.initials: SJ
authors.lastname: Foote
authors.forename: E
authors.initials: E
authors.lastname: Handman
mesh_terms: D000818:Animals; D020296:Animals, Congenic; D003433:Crosses, Genetic; D017931:DNA Primers; D004195:Disease Models, Animal; D005453:Fluorescence; D008040:Genetic Linkage / Q000235:genetics; D005838:Genotype; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics* / Q000378:metabolism; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D013045:Species Specificity; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D017931:DNA Primers; D015847:Interleukin-4; D007371:Interferon-gamma