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Dissociation of disease susceptibility, inflammation and cytokine profile in Imr1/2 congenic mice infected with Leishmania major

Citation

Elso, CM and Kumar, B and Smyth, G and Foote, SJ and Handman, E, Dissociation of disease susceptibility, inflammation and cytokine profile in Imr1/2 congenic mice infected with Leishmania major, Genes and Immunity, 5, (3) pp. 188-196 if. ISSN 1466-4879 (2004) [Refereed Article]

DOI: doi:10.1038/sj.gene.6364056

Abstract

Severity 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.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Clinical Sciences
Research Field:Infectious Diseases
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Infectious Diseases
Author:Foote, SJ (Professor Simon Foote)
ID Code:34962
Year Published:2004
Web of Science® Times Cited:13
Deposited By:Menzies Centre
Deposited On:2005-08-01
Last Modified:2007-05-29
Downloads:0

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