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Involvement of host cell integrin α2 in Cryptosporidium parvum infection
Haili Zhang1, Fengguang Guo, Guan Zhu
1Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, USA.
Abstract:
Cryptosporidium parvum is an opportunistic pathogen in AIDS patients. It is an intracellular but extracytoplasmic parasite residing in a host cell-derived parasitophorous vacuole. It is still poorly understood how this parasite interacts with host cells. We observed that expression of the integrin α2 (ITGA2) gene in host cells was significantly upregulated upon C. parvum infection, and a higher level of ITGA2 protein was present in the parasite infection sites. The infection could be reduced by the treatment of antibodies against ITGA2 and integrin β1 (ITGB1) subunits, as well as by type I collagen (an integrin α2β1 ligand). We also generated stable knockdown of ITGA2 gene expression in HCT-8 cells and observed consistent reduction of parasite infection in these knockdown cells. Collectively, our evidence indicates that host cell ITGA2 might be involved in interacting with Cryptosporidium during infection, probably acting as part of the regulatory elements upstream of the reported recruiting and reorganization of F actin at the infection sites.
Insights
Integrin alpha2 (ITGA2) on host cells is upregulated during Cryptosporidium parvum infection. Blocking ITGA2 or its ligand collagen reduces parasite entry, suggesting ITGA2
Area of Science:
- Immunology
- Cell Biology
- Parasitology
Background:
- Cryptosporidium parvum is an opportunistic pathogen impacting AIDS patients.
- The interaction mechanisms between C. parvum and host cells remain poorly understood.
- The parasite resides intracellularly but extracytoplasmically within a host cell-derived vacuole.
Purpose of the Study:
- To investigate the role of host cell molecules in C. parvum infection.
- To identify specific host cell components involved in parasite-host interactions.
Main Methods:
- Gene expression analysis of host cells upon C. parvum infection.
- Immunohistochemical detection of proteins at infection sites.
- Inhibition studies using antibodies against integrin subunits (ITGA2, ITGB1) and collagen.
- Stable knockdown of ITGA2 gene expression in HCT-8 cells.
Main Results:
- Integrin alpha2 (ITGA2) gene expression and protein levels were significantly upregulated at C. parvum infection sites.
- Treatment with anti-ITGA2 and anti-ITGB1 antibodies reduced parasite infection.
- Type I collagen, an ITGA2B1 ligand, also decreased infection levels.
- Stable knockdown of ITGA2 in HCT-8 cells resulted in reduced parasite infection.
Conclusions:
- Host cell ITGA2 plays a role in C. parvum infection.
- ITGA2 may mediate parasite interaction with host cells, potentially influencing actin reorganization at infection sites.
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