title: Hyperlipoproteinemia enhances susceptibility to acute disseminated Candida albicans infection in low-density-lipoprotein-receptor-deficient mice.
abstract: 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.
authors.affiliation: Department of Medicine, University Hospital Nijmegen, The Netherlands.
authors.forename: M G
authors.initials: MG
authors.lastname: Netea
authors.forename: P N
authors.initials: PN
authors.lastname: Demacker
authors.forename: N
authors.initials: N
authors.lastname: de Bont
authors.forename: O C
authors.initials: OC
authors.lastname: Boerman
authors.forename: A F
authors.initials: AF
authors.lastname: Stalenhoef
authors.forename: J W
authors.initials: JW
authors.lastname: van der Meer
authors.forename: B J
authors.initials: BJ
authors.lastname: Kullberg
mesh_terms: 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*
chemical_list: D016207:Cytokines; D011973:Receptors, LDL