Hyperlipoproteinemia enhances susceptibility to acute disseminated Candida albicans infection in low-density-lipoprotein-receptor-deficient mice.
Recent studies have suggested the use of lipoproteins as an adjuvant treatment of lethal gram-negative infections. However, other important microorganisms for the etiology of sepsis, such as Candida species, grow better in lipid-rich environments. We investigated the effect of hyperlipoproteinemia on systemic candidiasis in low-density-lipoprotein-receptor-deficient (LDLR-/-) mice, in which the loss of the receptor results in a seven- to ninefold-higher plasma LDL level than that in their wild-type littermates (C57BL/6J). LDLR-/- mice died earlier, and the outgrowth of Candida albicans in the kidneys and livers of LDLR-/- mice was significantly higher compared with that of controls. After infection, circulating cytokine concentrations were significantly higher in LDLR-/- mice. In vitro, C. albicans grew better in plasma samples of LDLR-/- mice than in control plasma samples and peritoneal macrophages of LDLR-/- mice challenged with heat-killed C. albicans produced more cytokines than did those of controls. This latter phenomenon was probably due to increased binding of yeast cells to macrophages of LDLR-/- mice. These data suggest that hyperlipoproteinemia is deleterious in systemic candidiasis.
Netea
M G
MG
Department of Medicine, University Hospital Nijmegen, The Netherlands.
Demacker
P N
PN
de Bont
N
N
Boerman
O C
OC
Stalenhoef
A F
AF
van der Meer
J W
JW
Kullberg
B J
BJ
D000208:Acute Disease; D000818:Animals; D002177:Candidiasis / Q000209:etiology*; D016207:Cytokines / Q000097:blood; D004198:Disease Susceptibility; D006801:Humans; D006951:Hyperlipoproteinemias / Q000150:complications*; D051379:Mice; D008810:Mice, Inbred C57BL; D011973:Receptors, LDL / Q000172:deficiency*
D016207:Cytokines; D011973:Receptors, LDL