The effect of
hyperlipoproteinemia on
systemic candidiasis was investigated by assessing the susceptibility of hyperlipoproteinemic,
apolipoprotein E (
ApoE)-deficient (
ApoE -/-) mice to a systemic Candida albicans
infection. The absence of
ApoE in these mice resulted in an eightfold increase in plasma
lipoprotein concentrations in the
very low-density lipoprotein (VLDL) fraction, as compared with levels seen in
ApoE +/+ mice. Mortality due to
candidemia was significantly higher (86%) in
ApoE -/- mice than in
ApoE+/+ mice (52%), and in platings of homogenized kidney material on fungal culture medium,
ApoE -/- mice yielded significantly higher levels of C. albicans outgrowth than did
ApoE+/+ mice. C albicans grew twofold better in
ApoE -/- plasma in 4 h than in
ApoE+/+ plasma, and depletion of
lipoproteins from plasma resulted in a significant seven- to tenfold increase in C. albicans growth. Recombinant
ApoE did not directly inhibit C. albicans growth. Our data indicate that the increased susceptibility of
ApoE -/- mice to C albicans is due both to increased growth of blastoconidia in
ApoE -/- mice in response to the availability of
lipids as nutrients, and to the neutralization of candidacidal factors by
lipoproteins. This study suggests that
lipoproteins play a significant role in host defense against
candidiasis.