Remnant lipoproteins inhibits malaria sporozoite invasion of hepatocytes

P. Sinnis, T. T. Willnow, M. R S Briones, J. Herz, V. Nussenzweig

Research output: Contribution to journalArticle

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Abstract

Remnants of lipoproteins, intestinal chylomicrons, and very low density lipoproteins (VLDL), are rapidly cleared from plasma and enter hepatocytes. It has been suggested that remnant lipoproteins are initially captured in the space of Disse by heparan sulfate proteoglycans (HSPGs), and that their subsequent internalization into hepatocytes is mediated by members of the LDL-receptor gene family. Similar to lipoprotein remnants, malaria sporozoites are removed from the blood circulation by the liver within minutes after injection by Anopheles mosquitoes. The sporozoite's surface is covered by the circumsporozoite protein (CS), and its region II-plus has been implicated in the binding of the parasites to glycosaminoglycan chains of hepatocyte HSPGs. Lactoferrin, a protein with antibacterial properties found in breast milk and neutrophil granules, is also rapidly cleared from the circulation by hepatocytes, and can inhibit the hepatic uptake of lipoprotein remnants. Here we provide evidence that sporozoites, lactoferrin, and remnant lipoproteins are cleared from the blood by similar mechanisms. CS, lactoferrin, and remnant lipoproteins compete in vitro and in vivo for binding sites on liver cells. The relevance of this binding event for sporozoite infectivity is highlighted by our demonstration that apoliprotein E-enriched β-VLDL and lactoferrin inhibit sporozoite invasion of HepG2 cells. In addition, malaria sporozoites are less infective in LDL-receptor knockout (LDLR-/-) mice maintained on a high fat diet, as compared with littermates maintained on a normal diet. We conclude that the clearance of lipoprotein remnants and sporozoites from the blood is mediated by the same set of highly sulfated HSPGs on the hepatocyte plasma membrane.

Original languageEnglish (US)
Pages (from-to)945-954
Number of pages10
JournalJournal of Experimental Medicine
Volume184
Issue number3
StatePublished - 1996

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Sporozoites
Lipoproteins
Malaria
Hepatocytes
Lactoferrin
Heparan Sulfate Proteoglycans
VLDL Lipoproteins
LDL Receptors
Liver
Chylomicrons
Proteins
Anopheles
Blood Circulation
Hep G2 Cells
High Fat Diet
Human Milk
Glycosaminoglycans
Culicidae
Knockout Mice
Parasites

ASJC Scopus subject areas

  • Immunology

Cite this

Sinnis, P., Willnow, T. T., Briones, M. R. S., Herz, J., & Nussenzweig, V. (1996). Remnant lipoproteins inhibits malaria sporozoite invasion of hepatocytes. Journal of Experimental Medicine, 184(3), 945-954.

Remnant lipoproteins inhibits malaria sporozoite invasion of hepatocytes. / Sinnis, P.; Willnow, T. T.; Briones, M. R S; Herz, J.; Nussenzweig, V.

In: Journal of Experimental Medicine, Vol. 184, No. 3, 1996, p. 945-954.

Research output: Contribution to journalArticle

Sinnis, P, Willnow, TT, Briones, MRS, Herz, J & Nussenzweig, V 1996, 'Remnant lipoproteins inhibits malaria sporozoite invasion of hepatocytes', Journal of Experimental Medicine, vol. 184, no. 3, pp. 945-954.
Sinnis, P. ; Willnow, T. T. ; Briones, M. R S ; Herz, J. ; Nussenzweig, V. / Remnant lipoproteins inhibits malaria sporozoite invasion of hepatocytes. In: Journal of Experimental Medicine. 1996 ; Vol. 184, No. 3. pp. 945-954.
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