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Infection and Immunity, October 2004, p. 6061-6067, Vol. 72, No. 10
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.10.6061-6067.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Cryptosporidium parvum at Different Developmental Stages Modulates Host Cell Apoptosis In Vitro

Raffaella Mele, Maria Angeles Gomez Morales, Fabio Tosini, and Edoardo Pozio*

Department of Infectious, Parasitic, and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy

Received 24 July 2003/ Returned for modification 14 December 2003/ Accepted 26 June 2004

We studied apoptosis in a human ileocecal adenocarcinoma tumor cell line (HCT-8) infected with Cryptosporidium parvum, from 2 to 72 h postinfection (h.p.i.). At 2 h.p.i., the percentage of annexin V-positive cells in the cell culture had increased to 10% compared to 2.5% in noninfected control culture; sorted infected cells expressed mRNA of FasL, the active form of caspase 3, and high caspase 3 activity, whereas the noninfected neighboring cells sorted from the same culture showed no signs of apoptosis. At 24 h.p.i., the percentages of early (annexin V positive) and late (DNA fragment) apoptotic cells were 13 and 2%, respectively, in the entire cell culture, and these percentages were not statistically significant in comparison with those from noninfected control cultures. At this time, sorted infected cells expressed the inactive form of caspase 3, a low caspase 3 activity, and the antiapoptotic protein Bcl-2. Noninfected cells sorted from the same culture showed expression of the active form of caspase 3, a moderate caspase 3 activity, and no Bcl-2 expression. At 48 h.p.i., the percentages of early and late apoptotic cells and caspase 3 activity had increased in the total cell culture, and both sorted infected and noninfected cells showed the active form of caspase 3. These results show that C. parvum, depending on its developmental stage, can inhibit (at the trophozoite stage) or promote (at the sporozoite and merozoite stages) host cell apoptosis, suggesting that it is able to interact with and regulate the host-cell gene expression.

* Corresponding author. Mailing address: Department of Infectious, Parasitic, and Immunomediated Diseases, Istituto Superiore di Sanità, viale Regina Elena 299, 00161 Rome, Italy. Phone: 39 06 4990 2304. Fax: 39 06 4938 7065. E-mail: pozio{at}iss.it.

Editor: J. F. Urban, Jr.

Infection and Immunity, October 2004, p. 6061-6067, Vol. 72, No. 10
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.10.6061-6067.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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