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Infection and Immunity, April 2008, p. 1738-1747, Vol. 76, No. 4
0019-9567/08/$08.00+0     doi:10.1128/IAI.01274-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Fibronectin Binding and Proteolytic Degradation by Leishmania and Effects on Macrophage Activation{triangledown}

Manjusha M. Kulkarni,1 Eric A. Jones,1 W. Robert McMaster,2 and Bradford S. McGwire1*

Division of Infectious Diseases and Center for Microbial Interface Biology, The Ohio State University, Columbus, Ohio,1 Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada2

Received 18 September 2007/ Returned for modification 31 October 2007/ Accepted 10 January 2008

Infection by vector-borne protozoa of the genus Leishmania occurs by the deposition of parasites within the skin of the mammalian host, where they eventually bind to and are phagocytized by M{phi}s. Our previous work supported the idea that parasites can interact with extracellular matrix and basement membrane proteins, such as fibronectin (FN), within the skin, leading to enhanced invasion. In this report, we extend these findings and show that both promastigotes and amastigotes of Leishmania species can bind directly to soluble FN and laminin (LM) and that promastigotes express a distinct surface protein of ~60 kDa that binds both FN and LM. Promastigotes of multiple Leishmania species can rapidly degrade FN by using surface-localized and secreted metalloprotease (leishmanolysin). FN degradation at the surfaces of amastigotes is leishmanolysin dependent, whereas both secreted leishmanolysin and cysteine protease B contribute to extracellular FN degradation. Leishmania-degraded FN decreased the production of reactive oxygen intermediates by parasite-infected macrophages and affected the accumulation of intracellular parasites. These findings show that both parasite stages of Leishmania species bind to and proteolytically degrade FN at the parasite surface and distantly through secreted proteases and that degraded forms of FN can influence the activation state of parasite-infected macrophages.

* Corresponding author. Mailing address: Division of Infectious Diseases and Center for Microbial Interface Biology, The Ohio State University Medical Center, Biomedical Research Tower, Rm. 1012, 460 W. 12th Ave., Columbus, OH 43210. Phone: (614) 292-3226. Fax: (614) 292-9616. E-mail: brad.mcgwire{at}osumc.edu

{triangledown} Published ahead of print on 22 January 2008.

Editor: W. A. Petri, Jr.

Infection and Immunity, April 2008, p. 1738-1747, Vol. 76, No. 4
0019-9567/08/$08.00+0     doi:10.1128/IAI.01274-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Halle, M., Gomez, M. A., Stuible, M., Shimizu, H., McMaster, W. R., Olivier, M., Tremblay, M. L. (2009). The Leishmania Surface Protease GP63 Cleaves Multiple Intracellular Proteins and Actively Participates in p38 Mitogen-activated Protein Kinase Inactivation. J. Biol. Chem. 284: 6893-6908 [Abstract] [Full Text]  


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