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Infection and Immunity, October 1999, p. 5282-5291, Vol. 67, No. 10
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Cryptosporidium parvum Apical Complex Glycoprotein CSL Contains a Sporozoite Ligand for Intestinal Epithelial Cells

Rebecca C. Langerdagger and Michael W. Riggs*

Department of Veterinary Science and Microbiology, University of Arizona, Tucson, Arizona 85721

Received 10 May 1999/Returned for modification 14 June 1999/Accepted 2 July 1999

Cryptosporidiosis, caused by the apicomplexan parasite Cryptosporidium parvum, has become a well-recognized diarrheal disease of humans and other mammals throughout the world. No approved parasite-specific drugs, vaccines, or immunotherapies for control of the disease are currently available, although passive immunization with C. parvum-specific antibodies has some efficacy in immunocompromised and neonatal hosts. We previously reported that CSL, an ~1,300-kDa conserved apical glycoprotein of C. parvum sporozoites and merozoites, is the antigenic species mechanistically bound by neutralizing monoclonal antibody 3E2 which elicits the circumsporozoite precipitate (CSP)-like reaction and passively protects against C. parvum infection in vivo. These findings indicated that CSL has a functional role in sporozoite infectivity. Here we report that CSL has properties consistent with being a sporozoite ligand for intestinal epithelial cells. For these studies, native CSL was isolated from whole sporozoites by isoelectric focusing (IEF) following observations that the ~1,300-kDa region containing CSL as seen by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was comprised of approximately 15 molecular species (pI 3 to 10) when examined by two-dimensional (2-D) electrophoresis and silver staining. A subset of six ~1,300-kDa species (pI 4.0 to 6.5) was specifically recognized by 3E2 in 2-D Western immunoblots of IEF-isolated CSL. Isolated native CSL bound specifically and with high affinity to permissive human intestinal epithelial Caco-2 cells in a dose-dependent, saturable, and self-displaceable manner. Further, CSL specifically bound to the surface of live Caco-2 cells inhibited sporozoite attachment and invasion. In addition, sporozoites having released CSL after incubation with 3E2 and occurrence of the CSP-like reaction did not attach to and invade Caco-2 cells. These findings indicate that CSL contains a sporozoite ligand which facilitates attachment to and invasion of Caco-2 cells and, further, that ligand function may be disrupted by CSL-reactive monoclonal antibody. We conclude that CSL is a rational target for passive or active immunization against cryptosporidiosis.

* Corresponding author. Mailing address: Department of Veterinary Science and Microbiology, Veterinary Science and Microbiology Building, Rm. 202, University of Arizona, Tucson, AZ 85721. Phone: (520) 621-2355. Fax: (520) 621-6366. E-mail: mriggs{at}u.arizona.edu.

dagger Present address: Center for Tropical Diseases, University of Texas, Galveston, TX 77555-0609.

Infection and Immunity, October 1999, p. 5282-5291, Vol. 67, No. 10
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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