UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Activation of transforming growth factor beta by malaria parasite-derived metalloproteinases and a thrombospondin-like molecule

Omer, FM; de Souza, JB; Corran, PH; Sultan, AA; Riley, EM; (2003) Activation of transforming growth factor beta by malaria parasite-derived metalloproteinases and a thrombospondin-like molecule. J EXP MED , 198 (12) 1817 - 1827. 10.1084/jem.20030713. Green open access

[img]
Preview
PDF
6944.pdf

Download (208kB)

Abstract

Much of the pathology of malaria is mediated by inflammatory cytokines (such as interleukin 12, interferon gamma, and tumor necrosis factor alpha), which are part of the immune response that kills the parasite. The antiinflammatory cytokine transforming growth factor (TGF)-beta plays a crucial role in preventing the severe pathology of malaria in mice and TGF-beta production is associated with reduced risk of clinical malaria in humans. Here we show that serum-free preparations of Plasmodium falciparum, Plasmodium yoelii 17XL, and Plasmodium berghei schizont-infected erythrocytes, but not equivalent preparations of uninfected erythrocytes, are directly able to activate latent TGF-beta (LatTGF-beta) in vitro. Antibodies to thrombospondin (TSP) and to a P. falciparum TSP-related adhesive protein (PfTRAP), and synthetic peptides from PfTRAP and P. berghei TRAP that represent homologues of TGF-beta binding motifis of TSP, all inhibit malaria-mediated TGF-beta activation. Importantly, TRAP-deficient P. berghei parasites are less able to activate LatTGF-beta than wild-type parasites and their replication is attenuated in vitro. We show that activation of TGF-beta by malaria parasites is a two step process involving TSP-like molecules and metalloproteinase activity. Activation of LatTGF-beta represents a novel mechanism for direct modulation of the host response by malaria parasites.

Type: Article
Title: Activation of transforming growth factor beta by malaria parasite-derived metalloproteinases and a thrombospondin-like molecule
Open access status: An open access version is available from UCL Discovery
DOI: 10.1084/jem.20030713
Keywords: parasitic protozoa, malaria, falciparum, transforming growth factor beta, matrix metalloproteinases, thrombospondin 1, PLASMODIUM-FALCIPARUM MALARIA, CHABAUDI-CHABAUDI INFECTION, NECROSIS-FACTOR-ALPHA, TGF-BETA, IN-VITRO, SCHISTOSOMA-MANSONI, CYTOKINE PRODUCTION, ANONYMOUS PROTEIN, GLIDING MOTILITY, ADHESIVE PROTEIN
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/6944
Downloads since deposit
711Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item