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Infection and Immunity, December 2004, p. 6806-6816, Vol. 72, No. 12
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.12.6806-6816.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Apical Organelle Discharge by Cryptosporidium parvum Is Temperature, Cytoskeleton, and Intracellular Calcium Dependent and Required for Host Cell Invasion

Xian-Ming Chen,1 Steven P. O'Hara,1 Bing Q. Huang,1 Jeremy B. Nelson,1 Jim Jung-Ching Lin,2 Guan Zhu,3 Honorine D. Ward,4 and Nicholas F. LaRusso1*

Center for Basic Research in Digestive Diseases, Division of Gastroenterology and Hepatology, Mayo Medical School, Clinic and Foundation, Rochester, Minnesota,1 Department of Biological Sciences, University of Iowa, Iowa City, Iowa,2 Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas,3 Division of Geographic Medicine and Infectious Diseases, Tufts-New England Medical Center, Boston, Massachusetts4

Received 1 July 2004/ Returned for modification 9 August 2004/ Accepted 13 August 2004

The apical organelles in apicomplexan parasites are characteristic secretory vesicles containing complex mixtures of molecules. While apical organelle discharge has been demonstrated to be involved in the cellular invasion of some apicomplexan parasites, including Toxoplasma gondii and Plasmodium spp., the mechanisms of apical organelle discharge by Cryptosporidium parvum sporozoites and its role in host cell invasion are unclear. Here we show that the discharge of C. parvum apical organelles occurs in a temperature-dependent fashion. The inhibition of parasite actin and tubulin polymerization by cytochalasin D and colchicines, respectively, inhibited parasite apical organelle discharge. Chelation of the parasite's intracellular calcium also inhibited apical organelle discharge, and this process was partially reversed by raising the intracellular calcium concentration by use of the ionophore A23187. The inhibition of parasite cytoskeleton polymerization by cytochalasin D and colchicine and the depletion of intracellular calcium also decreased the gliding motility of C. parvum sporozoites. Importantly, the inhibition of apical organelle discharge by C. parvum sporozoites blocked parasite invasion of, but not attachment to, host cells (i.e., cultured human cholangiocytes). Moreover, the translocation of a parasite protein, CP2, to the host cell membrane at the region of the host cell-parasite interface was detected; an antibody to CP2 decreased the C. parvum invasion of cholangiocytes. These data demonstrate that the discharge of C. parvum sporozoite apical organelle contents occurs and that it is temperature, intracellular calcium, and cytoskeleton dependent and required for host cell invasion, confirming that apical organelles play a central role in C. parvum entry into host cells.

* Corresponding author. Mailing address: Center for Basic Research in Digestive Diseases, Mayo Clinic, 200 First St., SW, Rochester, MN 55905. Phone: (507) 284-1006. Fax: (507) 284-0762. E-mail: larusso.nicholas{at}mayo.edu.

Editor: T. R. Kozel

Infection and Immunity, December 2004, p. 6806-6816, Vol. 72, No. 12
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.12.6806-6816.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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