Fetuin-A, a hepatocyte-specific protein that binds Plasmodium berghei thrombospondin-related adhesive protein: A potential role in infectivity

Deepa Jethwaney, Timothy Lepore, Saria Hassan, Kerrianne Mello, Radha Rangarajan, Willi Jahnen-Dechent, Dyann Wirth, Ali Sultan

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Malaria infection is initiated when the insect vector injects Plasmodium sporozoites into a susceptible vertebrate host. Sporozoites rapidly leave the circulatory system to invade hepatocytes, where further development generates the parasite form that invades and multiplies within erythrocytes. Previous experiments have shown that the thrombospondin-related adhesive protein (TRAP) plays an important role in sporozoite infectivity for hepatocytes. TRAP, a typical type-1 transmembrane protein, has a long extracellular region, which contains two adhesive domains, an A-domain and a thrombospondin repeat. We have generated recombinant proteins of the TRAP adhesive domains. These TRAP fragments show direct interaction with hepatocytes and inhibit sporozoite invasion in vitro. When the recombinant TRAP A-domain was used for immunoprecipitation against hepatocyte membrane fractions, it bound to α2-Heremans-Schmid glycoprotein/fetuin-A, a hepatocyte-specific protein associated with the extracellular matrix. When the soluble sporozoite protein fraction was immunoprecipitated on a fetuin-A-adsorbed protein A column, TRAP bound this ligand. Importantly, anti-fetuin-A antibodies inhibited invasion of hepatocytes by sporozoites. Further, onset of malaria infection was delayed in fetuin-A-deficient mice compared to that in wild-type C57BL/6 mice when they were challenged with Plasmodium berghei sporozoites. These data demonstrate that the extracellular region of TRAP interacts with fetuin-A on hepatocyte membranes and that this interaction enhances the parasite's ability to invade hepatocytes.

Original languageEnglish
Pages (from-to)5883-5891
Number of pages9
JournalInfection and Immunity
Volume73
Issue number9
DOIs
Publication statusPublished - Sep 2005
Externally publishedYes

Fingerprint

alpha-2-HS-Glycoprotein
Thrombospondins
Plasmodium berghei
Staphylococcal Protein A
Sporozoites
Adhesives
Hepatocytes
Proteins
Malaria
Parasites
Insect Vectors
Membranes
Plasmodium
Cardiovascular System
Infection
Inbred C57BL Mouse
Immunoprecipitation
Recombinant Proteins
Extracellular Matrix
Vertebrates

ASJC Scopus subject areas

  • Immunology

Cite this

Fetuin-A, a hepatocyte-specific protein that binds Plasmodium berghei thrombospondin-related adhesive protein : A potential role in infectivity. / Jethwaney, Deepa; Lepore, Timothy; Hassan, Saria; Mello, Kerrianne; Rangarajan, Radha; Jahnen-Dechent, Willi; Wirth, Dyann; Sultan, Ali.

In: Infection and Immunity, Vol. 73, No. 9, 09.2005, p. 5883-5891.

Research output: Contribution to journalArticle

Jethwaney, Deepa ; Lepore, Timothy ; Hassan, Saria ; Mello, Kerrianne ; Rangarajan, Radha ; Jahnen-Dechent, Willi ; Wirth, Dyann ; Sultan, Ali. / Fetuin-A, a hepatocyte-specific protein that binds Plasmodium berghei thrombospondin-related adhesive protein : A potential role in infectivity. In: Infection and Immunity. 2005 ; Vol. 73, No. 9. pp. 5883-5891.
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