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Leishmaniasis host response loci (lmr1–3) modify disease severity through a Th1/Th2-independent pathway

Genes & Immunity volume 5, pages 93–100 (2004)Cite this article

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.

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Acknowledgements

This work was supported by the National Institute of Health, USA, the Howard Hughes Medical Institute and the National Health and Medical Research Council, Australia. Colleen Elso was supported by an Australian Postgraduate Award. We thank Joan Curtis and Lynn Buckingham for technical assistance.

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Author notes

  1. S J Foote and E Handman: These authors have contributed equally to this work.

Authors and Affiliations

  1. The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia

    C M Elso, L J Roberts, G K Smyth, R J Thomson, T M Baldwin, S J Foote & E Handman

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  1. C M Elso
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  2. L J Roberts
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  3. G K Smyth
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  4. R J Thomson
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  7. E Handman
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Correspondence to S J Foote.

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Elso, C., Roberts, L., Smyth, G. et al. Leishmaniasis host response loci (lmr1–3) modify disease severity through a Th1/Th2-independent pathway. Genes Immun 5, 93–100 (2004). https://doi.org/10.1038/sj.gene.6364042

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