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Genetic analysis of innate immunity in resistance to Candida albicans

Abstract

Systemic candidiasis is a significant cause of nosocomial infections and the mechanisms of defense against Candida albicans in humans remain poorly understood. Studies in animal models have demonstrated the importance of innate immunity in controlling the response to infection. Although Th1 cytokines have been shown to direct the overall outcome of infection, the precise role of the Th1/Th2 response and, more generally, the adaptive immune response as a whole, in systemic candidiasis, appears to apply mainly to the development of resistance to reinfection. A genetic approach to the identification of host factors regulating pathogenesis and susceptibility to C. albicans infection has been used in humans and in mouse models of infection. Mouse mutants bearing experimentally induced mutations in specific genes have provided a systematic tool for directly assessing the role of individual proteins in C. albicans susceptibility. Inbred mouse strains have been valuable in showcasing the spectrum of naturally occurring variations in initial susceptibility to infection, and type of disease developed. Crosses between resistant and susceptible strains have led to the detection of additional gene effects affecting innate immunity. Of particular interest is the major effect of a naturally occurring loss-of-function mutation in the C5 complement component that has become fixed in many inbred strains. These and other studies have shown that both a functional complement pathway and robust inflammatory response are critical for resistance to C. albicans.

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Acknowledgements

PG is a distinguished scientist of the Canadian Institutes of Health Research and a James McGill Professor. AT is supported by a studentship from the Natural Sciences and Engineering Research Council of Canada. This work was supported by the Genomics and Health Initiative of the National Research Council of Canada. This is an NRC publication number 37729.

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Tuite, A., Mullick, A. & Gros, P. Genetic analysis of innate immunity in resistance to Candida albicans. Genes Immun 5, 576–587 (2004). https://doi.org/10.1038/sj.gene.6364130

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  • DOI: https://doi.org/10.1038/sj.gene.6364130

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