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Genetic control of suceptibility to Candida albicans in susceptible A/J and resistant C57BL/6J mice

Genes & Immunity volume 6, pages 672–682 (2005)Cite this article

Abstract

The importance of host factors in determining susceptibility to systemic Candida albicans infections is evident in both humans and mice. We have used a mouse model to study the genetic basis of susceptibility, using the inbred strains A/J and C57BL/6J, which are susceptible and resistant, respectively, based on different parameters of the response to infection. To identify genes responsible for this differential host response, brain and kidney fungal load were measured in 128 [A/J × C57BL/6J] F2 mice 48 h after infection with 5 × 104 C. albicans blastospores. Segregation analysis in this informative population identified complement component 5 (C5/Hc) as the major gene responsible for this differential susceptibility (LOD of 22.7 for kidney, 19.0 for brain), with a naturally occurring mutation that causes C5 deficiency leading to enhanced susceptibility. C5 was also found to control heart fungal load, survival time, and serum TNF-α levels during infection. Investigation of the response to C. albicans challenge in a series of AcB/BcA recombinant congenic strains validated the importance of C5 in determining the host response. However, the strains BcA67 and BcA72 showed discordant phenotypes with respect to their C5 status, suggesting additional complexity in the genetic control of the inter-strain difference in susceptibility observed in A/J and C57BL/6J following systemic infection with C. albicans.

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Acknowledgements

This work was supported by research grants from the Canadian Genetic Diseases Network to PG. PG is a James McGill Professor of Biochemistry and is a distinguished Investigator of the Canadian Institutes of Health Research. AT is supported by a studentship from the Natural Sciences and Engineering Research Council of Canada. Work in AM's lab was supported by the Genomics and Health Initiative of the National research Council of Canada.

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Authors and Affiliations

  1. Department of Biochemistry, Center for the Study of Host Resistance, McGill University, Montreal, Quebec, Canada

    A Tuite & P Gros

  2. Biotechnology Research Institute, Montreal, Quebec, Canada

    M Elias, S Picard & A Mullick

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  1. A Tuite
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  2. M Elias
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  3. S Picard
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  4. A Mullick
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Correspondence to P Gros.

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Tuite, A., Elias, M., Picard, S. et al. Genetic control of suceptibility to Candida albicans in susceptible A/J and resistant C57BL/6J mice. Genes Immun 6, 672–682 (2005). https://doi.org/10.1038/sj.gene.6364254

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