Genetics of resistance to infection with Candida albicans in mice

Abstract

To determine differences in susceptibility, 234 naive mice including xid and beige mutants were infected intravenously with Candida albicans and monitored with survival analysis and quantitative culture of the kidneys. By using survival time as the criterion, animals of seven inbred strains were separated into three groups. C3H/HeJ and Dw/+ were most susceptible; C57BR/cdJ, BRVR and CBA/N (xid) were intermediate in susceptibility; C57BL/KsJ and C57BL/6J were least susceptible. Mean survival times (MST) were markedly influenced by the number of Candida cells injected while the ranking of mouse strains by survival alone was unchanged. There was a dissimilar behaviour of the strains to produce organ weight changes in response to infection when compared with uninfected mice which were matched for age and genetic lineage. Black mice had lower colony forming units (CFU) per mg of tissue at the time of death than animals of other genetic lineage. Nevertheless, the finding that MST and CFU studies were loosely correlated in a few strains of mice indicated that the proliferation of the fungus in the kidneys was not always the major cause of death. The beige mutation was found to determine an increased susceptibility to systemic Candida infection. The differences in survival for beige and nonbeige mice were influenced by the genetic lineage of the host, being much greater in the C57BL/6 strain (36.7 days) than in the C3H/He strain (5 days). C57BL/6 beige-J had significantly higher CFU per organ and per unit of weight than C57BL/6 +/+ mice. These data evinced an important contribution of host genetic factors to resistance to systemic candidiasis. It is suggested that innate resistance genes regulate the differentiation in the bone marrow and the function of cells of granulocyte-macrophage lineage.