MicroRNA-221 controls expression of intercellular adhesion molecule-1 in epithelial cells in response to Cryptosporidium parvum infection

Abstract

Cryptosporidium parvum is a protozoan parasite that infects gastrointestinal epithelial cells and causes diarrheal disease in humans and animals globally. Pathological changes following C. parvum infection include crypt hyperplasia, a modest inflammatory reaction with increased infiltration of lymphocytes into intestinal mucosa. Expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), on infected epithelial cell surfaces may facilitate adhesion and recognition of lymphocytes at infection sites. MicroRNAs (miRNAs) are small RNA molecules of 23 nucleotides that negatively regulate protein-coding gene expression via translational suppression or mRNA degradation. We recently reported that microRNA-221 (miR-221) regulates ICAM-1 translation through targeting the ICAM-1 3′-untranslated region (UTR). In this study, we tested the role of miR-221 in regulating ICAM-1 expression in epithelial cells in response to C. parvum infection using an in vitro model of human biliary cryptosporidiosis. Up-regulation of ICAM-1 at both message and protein levels was detected in epithelial cells following C. parvum infection. Inhibition of ICAM-1 transcription with actinomycin D could only partially block C. parvum-induced ICAM-1 expression at the protein level. Cryptosporidium parvum infection decreased miR-221 expression in infected epithelial cells. When cells were transfected with a luciferase reporter construct covering the miR-221 binding site in the ICAM-1 3′-UTR and then exposed to C. parvum, an enhanced luciferase activity was detected. Transfection of miR-221 precursor abolished C. parvum-stimulated ICAM-1 protein expression. In addition, expression of ICAM-1 on infected epithelial cells facilitated epithelial adherence of co-cultured Jurkat cells. These results indicate that miR-221-mediated translational suppression controls ICAM-1 expression in epithelial cells in response to C. parvum infection.

Dectin-1 is required for miR155 upregulation in murine macrophages in response toCandida albicans

“…Of note, BMDMs interacting with hyphae also increased their levels of other miRNAs, including 125b, miR132, miR199, and miR223. While these miRNAs have been associated with responses to other pathogens 18,[46][47][48] , this is the first report demonstrating their specific induction by C. albicans. Upon activation of a host effector cell by a microbe, miRNAs are induced and commonly act as regulators, modulating the host response.…”

“…These targets are often components of key steps of PRR pathways, transcriptional factors or cytokines. For instance, miR9, miR199, miR221 and miR223 exert a regulatory activity on inflammation [48][49][50][51] . miR146 impairs proinflammatory cytokines in dendritic cells by targeting the mRNAs of the TLR pathway proteins TRAF6 and IRAK1 19,52 .…”

Circulating MicroRNAs in Patients with Active Pulmonary Tuberculosis

“…Besides being involved in carcinogenesis, miR-221* also was involved in infection and was decreased in epithelial cells in response to Cryptosporidium parvum infection (9). miR-511 was identified as a novel potent modulator of human immune response and as a positive regulator of Toll-like receptor 4 (28).…”

MicroRNAs in parasitic diseases: Potential for diagnosis and targeting

“…In this respect, it has been already shown that several apicomplexan parasites, some of them already mentioned -Cryptosporidium parvum, Plasmodium spp., Eimeria tenella and T. gondii -can modulate miRNA populations in their hosts and induce changes in the expression of regulatory immune molecules in host cells, some of them associated with protective immunity [54][55][56]. Several of these authors suggest that the regulatory process takes place via an active mechanism controlled by the invading parasite.…”