Differential susceptibility to Candida albicans in mice

C5-deficiency in the A/J and recombinant congenic strain, BcA17, is linked to a dysregulated inflammatory response to Candida albicans infection and high morbidity compared to C5-sufficient C57Bl/6J (B6) mice. The recombinant congenic BcA70 strain thus provides an ideal model to study the effect of C5-deficiency on a B6 genetic background. We have used the A/J and BcA70 strains to carry out a detailed analysis of the pathophysiological effects of the uncontrolled inflammatory activity as a result of Candida infection. We present several lines of evidence to indicate that the heart of C5-deficient mice is severely affected by infection, although the kidney is the site of highest fungal replication. Histological sections of Candida-infected cardiac and kidney tissues from A/J mice reveal cellular infiltration in the vicinity of hyphal foci in the heart, leaving more dense fungal colonies in the kidney unaffected. As well as high-level inflammatory activity in the infected heart tissue, gene expression profiles revealed a striking lack of cardio-protective stress response linked to C5-deficiency. An inability of the A/J and BcA17 hearts to make the appropriate adaptive changes resulted in lower levels of both fatty acid and glucose metabolism, leading to cardiac failure. Keywords: differential response to infection; genetic variation 4 biological replicates were used for each strain for both uninfected and infected samples and BcA70 was hybridized against control C57Bl/6 on chip. Dye swaps were included and normalization was performed using dye swap correction and intensity dependent normalization on GeneSpring.