Genetic determination of susceptibility and resistance in the pathogenesis of Candida albicans infection.

Abstract

The concepts of susceptibility and resistance are central to both clinical and experimental studies of infectious diseases. In general, resistance implies survival rather than death, or at the very least, a marked reduction in the severity of symptoms when compared with susceptible individuals. It is usually associated with the presence in the host of particular alleles of one or more genes that contribute to the formation of a ‘resistant’ phenotype. Conversely, susceptibility is determined by the presence of the ‘susceptible’ alleles of these genes. Diseases associated with Candida albicans infection occur in two discrete forms, mucosal and systemic. Mild infections of the oral and vaginal mucosa are common in the general population, but they are seen most frequently, and in their most severe form, in individuals with defects in the cell-mediated immune response. On the other hand, systemic candidiasis is confined almost exclusively to debilitated or immunocompromised patients in the hospital environment. Although a propensity to exploit flaws in host defence mechanisms in order to establish infection is certainly not unique to C. albicans , these clinical correlations may not offer relevant insights into the disease process, as deficiencies in host defence mechanisms induced by drugs or disease will not necessarily reflect the effector pathways that determine susceptibility and resistance to infection in the unmodified host. The object of this review is to highlight various aspects of susceptibility to C. albicans infection in both humans and experimental animals, and by examining recent studies of genetic influences on host responses, to propose a new paradigm for the experimental analysis of the mechanisms of pathogenesis. Our understanding of the pathogenesis of C. albicans infection in humans is confused by the multitude of factors that can precipitate infections, and the different sites at which they can occur. In healthy men and women, ‘conversion’ …