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Infection and Immunity, February 2008, p. 750-758, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.01104-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Sequence Diversity of the Trypanosoma cruzi Complement Regulatory Protein Family{triangledown} ,{dagger}

M. Beucher* and K. A. Norris

Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15237

Received 8 August 2007/ Returned for modification 24 September 2007/ Accepted 19 November 2007

As a central component of innate immunity, complement activation is a critical mechanism of containment and clearance of microbial pathogens in advance of the development of acquired immunity. Several pathogens restrict complement activation through the acquisition of host proteins that regulate complement activation or through the production of their own complement regulatory molecules (M. K. Liszewski, M. K. Leung, R. Hauhart, R. M. Buller, P. Bertram, X. Wang, A. M. Rosengard, G. J. Kotwal, and J. P. Atkinson, J. Immunol. 176:3725-3734, 2006; J. Lubinski, L. Wang, D. Mastellos, A. Sahu, J. D. Lambris, and H. M. Friedman, J. Exp. Med. 190:1637-1646, 1999). The infectious stage of the protozoan parasite Trypanosoma cruzi produces a surface-anchored complement regulatory protein (CRP) that functions to inhibit alternative and classical pathway complement activation (K. A. Norris, B. Bradt, N. R. Cooper, and M. So, J. Immunol. 147:2240-2247, 1991). This study addresses the genomic complexity of the T. cruzi CRP and its relationship to the T. cruzi supergene family comprising active trans-sialidase (TS) and TS-like proteins. The TS superfamily consists of several functionally distinct subfamilies that share a characteristic sialidase domain at their amino termini. These TS families include active TS, adhesions, CRPs, and proteins of unknown functions (G. A. Cross and G. B. Takle, Annu. Rev. Microbiol. 47:385-411, 1993). A sequence comparison search of GenBank using BLASTP revealed several full-length paralogs of CRP. These proteins share significant homology at their amino termini and a strong spatial conservation of cysteine residues. Alternative pathway complement regulation was confirmed for CRP paralogs with 58% (low) and 83% (high) identity to AAB49414. CRPs are functionally similar to the microbial and mammalian proteins that regulate complement activation. Sequence alignment of mammalian complement control proteins to CRP showed that these sequences are distinct, supporting a convergent evolutionary pathway. Finally, we show that a clonal line of T. cruzi expresses multiple unique copies of CRP that are differentially recognized by patient sera.

* Corresponding author. Mailing address: Department of Immunology E1004, University of Pittsburgh School of Medicine, Pittsburgh, PA 15237. Phone: (412) 648-0293. Fax: (412) 383-8096. E-mail: beucher1{at}pitt.edu

{triangledown} Published ahead of print on 10 December 2007.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: W. A. Petri, Jr.

Infection and Immunity, February 2008, p. 750-758, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.01104-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Antoine-Moussiaux, N., Buscher, P., Desmecht, D. (2009). Host-Parasite Interactions in Trypanosomiasis: on the Way to an Antidisease Strategy. Infect. Immun. 77: 1276-1284 [Full Text]  


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