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. 1997 Jul;65(7):2663–2667. doi: 10.1128/iai.65.7.2663-2667.1997

Hyperlipoproteinemia enhances susceptibility to acute disseminated Candida albicans infection in low-density-lipoprotein-receptor-deficient mice.

M G Netea 1, P N Demacker 1, N de Bont 1, O C Boerman 1, A F Stalenhoef 1, J W van der Meer 1, B J Kullberg 1
PMCID: PMC175376  PMID: 9199434

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.

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Selected References

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  1. Beutler B., Milsark I. W., Cerami A. C. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science. 1985 Aug 30;229(4716):869–871. doi: 10.1126/science.3895437. [DOI] [PubMed] [Google Scholar]
  2. Cannon J. G., Tompkins R. G., Gelfand J. A., Michie H. R., Stanford G. G., van der Meer J. W., Endres S., Lonnemann G., Corsetti J., Chernow B. Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever. J Infect Dis. 1990 Jan;161(1):79–84. doi: 10.1093/infdis/161.1.79. [DOI] [PubMed] [Google Scholar]
  3. D'Angio R., Quercia R. A., Treiber N. K., McLaughlin J. C., Klimek J. J. The growth of microorganisms in total parenteral nutrition admixtures. JPEN J Parenter Enteral Nutr. 1987 Jul-Aug;11(4):394–397. doi: 10.1177/0148607187011004394. [DOI] [PubMed] [Google Scholar]
  4. Djeu J. Y., Blanchard D. K., Halkias D., Friedman H. Growth inhibition of Candida albicans by human polymorphonuclear neutrophils: activation by interferon-gamma and tumor necrosis factor. J Immunol. 1986 Nov 1;137(9):2980–2984. [PubMed] [Google Scholar]
  5. Esfahani M., Bigler R. D., Alfieri J. L., Lund-Katz S., Baum J. D., Scerbo L. Cholesterol regulates the cell surface expression of glycophospholipid-anchored CD14 antigen on human monocytes. Biochim Biophys Acta. 1993 Jul 4;1149(2):217–223. doi: 10.1016/0005-2736(93)90204-d. [DOI] [PubMed] [Google Scholar]
  6. Fraker P. J., Speck J. C., Jr Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun. 1978 Feb 28;80(4):849–857. doi: 10.1016/0006-291x(78)91322-0. [DOI] [PubMed] [Google Scholar]
  7. Gilbert M., Gallagher S. C., Eads M., Elmore M. F. Microbial growth patterns in a total parenteral nutrition formulation containing lipid emulsion. JPEN J Parenter Enteral Nutr. 1986 Sep-Oct;10(5):494–497. doi: 10.1177/0148607186010005494. [DOI] [PubMed] [Google Scholar]
  8. Hazen K. C. Participation of yeast cell surface hydrophobicity in adherence of Candida albicans to human epithelial cells. Infect Immun. 1989 Jul;57(7):1894–1900. doi: 10.1128/iai.57.7.1894-1900.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hubsch A. P., Powell F. S., Lerch P. G., Doran J. E. A reconstituted, apolipoprotein A-I containing lipoprotein reduces tumor necrosis factor release and attenuates shock in endotoxemic rabbits. Circ Shock. 1993 May;40(1):14–23. [PubMed] [Google Scholar]
  10. Ishibashi S., Brown M. S., Goldstein J. L., Gerard R. D., Hammer R. E., Herz J. Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery. J Clin Invest. 1993 Aug;92(2):883–893. doi: 10.1172/JCI116663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jeremias J., Kalo-Klein A., Witkin S. S. Individual differences in tumour necrosis factor and interleukin-1 production induced by viable and heat-killed Candida albicans. J Med Vet Mycol. 1991;29(3):157–163. doi: 10.1080/02681219180000261. [DOI] [PubMed] [Google Scholar]
  12. Jouault T., Lepage G., Bernigaud A., Trinel P. A., Fradin C., Wieruszeski J. M., Strecker G., Poulain D. Beta-1,2-linked oligomannosides from Candida albicans act as signals for tumor necrosis factor alpha production. Infect Immun. 1995 Jun;63(6):2378–2381. doi: 10.1128/iai.63.6.2378-2381.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kullberg B. J., van 't Wout J. W., van Furth R. Role of granulocytes in increased host resistance to Candida albicans induced by recombinant interleukin-1. Infect Immun. 1990 Oct;58(10):3319–3324. doi: 10.1128/iai.58.10.3319-3324.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lawrence J., Turner M., Gilbert P. Microbial contamination and growth in total parenteral nutrition solutions. J Clin Pharm Ther. 1988 Apr;13(2):151–157. doi: 10.1111/j.1365-2710.1988.tb00172.x. [DOI] [PubMed] [Google Scholar]
  15. Levine D. M., Parker T. S., Donnelly T. M., Walsh A., Rubin A. L. In vivo protection against endotoxin by plasma high density lipoprotein. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):12040–12044. doi: 10.1073/pnas.90.24.12040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lynn W. A., Cohen J. Adjunctive therapy for septic shock: a review of experimental approaches. Clin Infect Dis. 1995 Jan;20(1):143–158. doi: 10.1093/clinids/20.1.143. [DOI] [PubMed] [Google Scholar]
  17. Murthy A. R., Lehrer R. I., Harwig S. S., Miyasaki K. T. In vitro candidastatic properties of the human neutrophil calprotectin complex. J Immunol. 1993 Dec 1;151(11):6291–6301. [PubMed] [Google Scholar]
  18. Netea M. G., Blok W. L., Kullberg B. J., Bemelmans M., Vogels M. T., Buurman W. A., van der Meer J. W. Pharmacologic inhibitors of tumor necrosis factor production exert differential effects in lethal endotoxemia and in infection with live microorganisms in mice. J Infect Dis. 1995 Feb;171(2):393–399. doi: 10.1093/infdis/171.2.393. [DOI] [PubMed] [Google Scholar]
  19. Netea M. G., Demacker P. N., Kullberg B. J., Boerman O. C., Verschueren I., Stalenhoef A. F., van der Meer J. W. Low-density lipoprotein receptor-deficient mice are protected against lethal endotoxemia and severe gram-negative infections. J Clin Invest. 1996 Mar 15;97(6):1366–1372. doi: 10.1172/JCI118556. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Parrillo J. E. Pathogenetic mechanisms of septic shock. N Engl J Med. 1993 May 20;328(20):1471–1477. doi: 10.1056/NEJM199305203282008. [DOI] [PubMed] [Google Scholar]
  21. Read T. E., Grunfeld C., Kumwenda Z. L., Calhoun M. C., Kane J. P., Feingold K. R., Rapp J. H. Triglyceride-rich lipoproteins prevent septic death in rats. J Exp Med. 1995 Jul 1;182(1):267–272. doi: 10.1084/jem.182.1.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rothberg K. G., Ying Y. S., Kamen B. A., Anderson R. G. Cholesterol controls the clustering of the glycophospholipid-anchored membrane receptor for 5-methyltetrahydrofolate. J Cell Biol. 1990 Dec;111(6 Pt 2):2931–2938. doi: 10.1083/jcb.111.6.2931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. States B., Segal S. Levels of gamma-glutamyltranspeptidase in cultured skin fibroblasts from cystinotics and normals. Life Sci. 1980 Nov 24;27(21):1985–1990. doi: 10.1016/0024-3205(80)90419-1. [DOI] [PubMed] [Google Scholar]
  24. Steinshamn S., Waage A. Tumor necrosis factor and interleukin-6 in Candida albicans infection in normal and granulocytopenic mice. Infect Immun. 1992 Oct;60(10):4003–4008. doi: 10.1128/iai.60.10.4003-4008.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tracey K. J., Fong Y., Hesse D. G., Manogue K. R., Lee A. T., Kuo G. C., Lowry S. F., Cerami A. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature. 1987 Dec 17;330(6149):662–664. doi: 10.1038/330662a0. [DOI] [PubMed] [Google Scholar]
  26. Ulevitch R. J., Johnston A. R. The modification of biophysical and endotoxic properties of bacterial lipopolysaccharides by serum. J Clin Invest. 1978 Dec;62(6):1313–1324. doi: 10.1172/JCI109252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Vecchiarelli A., Todisco T., Puliti M., Dottorini M., Bistoni F. Modulation of anti-Candida activity of human alveolar macrophages by interferon-gamma or interleukin-1-alpha. Am J Respir Cell Mol Biol. 1989 Jul;1(1):49–55. doi: 10.1165/ajrcmb/1.1.49. [DOI] [PubMed] [Google Scholar]
  28. Wakabayashi G., Gelfand J. A., Burke J. F., Thompson R. C., Dinarello C. A. A specific receptor antagonist for interleukin 1 prevents Escherichia coli-induced shock in rabbits. FASEB J. 1991 Mar 1;5(3):338–343. doi: 10.1096/fasebj.5.3.1825816. [DOI] [PubMed] [Google Scholar]
  29. Wey S. B., Mori M., Pfaller M. A., Woolson R. F., Wenzel R. P. Hospital-acquired candidemia. The attributable mortality and excess length of stay. Arch Intern Med. 1988 Dec;148(12):2642–2645. doi: 10.1001/archinte.148.12.2642. [DOI] [PubMed] [Google Scholar]
  30. Yeaman M. R., Ibrahim A. S., Edwards J. E., Jr, Bayer A. S., Ghannoum M. A. Thrombin-induced rabbit platelet microbicidal protein is fungicidal in vitro. Antimicrob Agents Chemother. 1993 Mar;37(3):546–553. doi: 10.1128/aac.37.3.546. [DOI] [PMC free article] [PubMed] [Google Scholar]

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