Apolipoprotein-E-deficient mice exhibit an increased susceptibility to disseminated candidiasis.
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.
Division of General Internal Medicine, Department of Medicine, University Medical Center, Nijmegen, The Netherlands.
Alieke G
AG
Vonk
Natasja
N
De Bont
Mihai G
MG
Netea
Pierre N M
PN
Demacker
Jos W M
JW
van der Meer
Anton F H
AF
Stalenhoef
Bart Jan
BJ
Kullberg
D000818:Animals; D001057:Apolipoproteins E / Q000097:blood / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002176:Candida albicans / Q000254:growth & development / Q000472:pathogenicity*; D002177:Candidiasis / Q000235:genetics* / Q000382:microbiology / Q000401:mortality / Q000503:physiopathology*; D016469:Fungemia / Q000382:microbiology / Q000401:mortality; D020022:Genetic Predisposition to Disease; D006951:Hyperlipoproteinemias / Q000150:complications; D008079:Lipoproteins, VLDL / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL
D001057:Apolipoproteins E; D008079:Lipoproteins, VLDL