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Dissociation of disease susceptibility, inflammation and cytokine profile in Imr1/2 congenic mice infected with Leishmania major
journal contribution
posted on 2023-05-16, 16:46 authored by Elso, CM, Kumar, B, Smyth, G, Simon James FooteSimon James Foote, Handman, ESeverity of disease caused by Leishmania major depends on the genetics of the host. Early induction of T helper cell type 1 (Th1)-type responses in resistant C57BL/6 mice and T helper cell type 2 (Th2) in susceptible BALB/c mice is thought to determine cure or disease respectively. We have mapped three loci that confer susceptibility or resistance upon congenic mice on the C57BL/6 or BALB/c backgrounds. Here we examine the histopathology and production of interleukin 4 (IL-4) and interferon gamma (IFN-γ) in the skin and draining lymph nodes in the congenic and parental mice. We show an evolving granuloma with a staged infiltration of inflammatory cells, but no difference between the groups. As an indication of an early-polarised Th1/Th2 response we measured IFN-γ and IL-4 in the lymph nodes and found no difference between any of the mice during the first 48 h. During infection, the level of IL-4 correlated with the lesion size, indicating that IL-4 reflects the disease severity rather than controls it. Considering this effect, B6.C(lmr1,lmr2) mice had similar cytokine levels to the parental C57BL/6 mice despite increased susceptibility and C.B6(lmr1,lmr2) were similar to BALB/c despite increased resistance. We conclude that the lmr loci affect disease severity by a mechanism independent of conventional helper T-cell responses. © 2004 Nature Publishing Group All rights reserved.
History
Publication title
Genes and ImmunityVolume
5Pagination
188-196 ifISSN
1466-4879Department/School
Menzies Institute for Medical ResearchPublisher
Nature Publishing GroupPlace of publication
USARepository Status
- Restricted