Cryptosporidium parvumat Different Developmental Stages Modulates Host Cell Apoptosis In Vitro

Abstract

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.

The Human Immunodeficiency Virus Type 1 Tat Protein EnhancesCryptosporidium parvum-Induced Apoptosis in Cholangiocytes via a Fas Ligand-Dependent Mechanism

“…In accordance with previous reports (14,37) The mechanisms by which FasL is translocated to the membrane and released from infected cells are unclear and currently under investigation. C. parvum activates kinase pathways in infected cells (10,11,16); we recently demonstrated that there is recruitment of transporters and channels to the site of infection (15), consistent with the active recruitment of vesicles to the plasma membrane.…”

Development of Cryptosporidium parvum-Induced Gastrointestinal Neoplasia in Severe Combined Immunodeficiency (SCID) Mice: Severity of Lesions Is Correlated with Infection Intensity

“…In 6/16 animals (37.5%) (mice nos. 7,8,15,16,24, and 32), lesions were detected in more than one organ with a maximum score of histologic severity of 11 in mouse no. 16 ( Table 1 ).…”

“…In addition, we showed that deep immunosuppression alone did not entail neoplasia in uninfected hosts. Taking into account that C. parvum is able to modulate apoptosis of intestinal cells during its replication, 7 a mechanism known to be involved in the carcinogenesis processes, 8 and that SCID mice developed a chronic C. parvum infection with dose-dependent pathologic effects, 9 we further studied C. parvum -induced gastrointestinal neoplasia using variable doses of C. parvum inocula and the cell proliferation marker Ki-67. The Ki-67 nuclear antigen has been shown to be expressed in proliferating cells during G 1 , S, G 2 , and mitosis stages of the cell cycle.…”

Prevalence of Cryptosporidium sp. In Patients with Colorectal Cancer

“…The International Agency for Research on Cancer (IARC) has also deemed Opisthorchis viverrini and Clonorchis sinensis infections to be carcinogenic factors in the development of biliary tract cancer (24). Those chronic parasitoses may affect apoptosis and DNA repair disturbances (25,26).…”