Dissociation of disease susceptibility, inflammation and cytokine profile in lmr1/2 congenic mice infected with Leishmania major
Details
Publication Year 2004-05,Volume 5,Issue #3,Page 188-196
Journal Title
GENES AND IMMUNITY
Publication Type
Journal Article
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-gamma) 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-gamma 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.
Publisher
NATURE PUBLISHING GROUP
Keywords
MURINE CUTANEOUS LEISHMANIASIS; T-CELL SUBSETS; BALB/C MICE; PROGRESSIVE DISEASE; MULTIPLE LOCI; TH2 RESPONSE; IL-4; RESISTANCE; INTERLEUKIN-4; EXPRESSION
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Creation Date: 2004-05-01 12:00:00
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