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Trypanosoma cruzi uses a 45-kDa mucin for adhesion to mammalian cells
Corey W Turner1, Maria F Lima, Fernando Villalta
1Department of Microbiology, School of Medicine, Meharry Medical College, 1005 D.B. Todd Jr. Boulevard, Nashville, TN 37208, USA.
Abstract:
A set of monoclonal antibodies that recognizes a Trypanosoma cruzi 45-kDa protein was produced and used to characterize this molecule and study its role in trypanosome adhesion to heart myoblasts. We found that the 45-kDa protein is a surface mucin, is expressed only in invasive trypomastigotes, but not in noninvasive epimastigotes or amastigotes, and is released by the trypanosome in culture medium. One of the monoclonal antibodies (Mab B5) from this set inhibits the attachment of trypomastigotes to heart myoblasts preventing trypanosome entry, whereas the others (Mabs B4 and F1) do not. This inhibition was seen with the B5 hybridoma culture supernatant, with the purified Mab B5 IgG or with Mab B5 Fab fragments. These novel findings identify the 45-kDa mucin as a new T. cruzi ligand that is used by invasive forms of this organism to adhere to heart myoblasts.
Insights
Researchers identified a Trypanosoma cruzi 45-kDa surface mucin crucial for parasite adhesion to heart cells. A specific antibody blocks this interaction, preventing cell entry, highlighting a potential therapeutic target.
Area of Science:
- Parasitology
- Immunology
- Molecular Biology
Background:
- Trypanosoma cruzi causes Chagas disease, a significant global health concern.
- Understanding parasite-host interactions is key to developing effective treatments.
- Specific parasite molecules mediating adhesion to host cells remain largely uncharacterized.
Purpose of the Study:
- To characterize a Trypanosoma cruzi 45-kDa surface protein.
- To investigate the role of this protein in trypanosome adhesion to heart myoblasts.
- To identify potential targets for blocking parasite invasion.
Main Methods:
- Production of monoclonal antibodies against the 45-kDa protein.
- Characterization of the protein's localization and expression patterns.
- In vitro adhesion assays using monoclonal antibodies and purified immunoglobulin G (IgG) or fragments (Fab).
Main Results:
- The 45-kDa protein is a surface mucin expressed only in invasive trypomastigotes.
- This protein is released into the culture medium by the trypanosome.
- One monoclonal antibody (Mab B5) significantly inhibited trypanosome attachment and subsequent entry into heart myoblasts.
Conclusions:
- The 45-kDa mucin is a novel ligand mediating Trypanosoma cruzi adhesion to heart cells.
- Mab B5 effectively blocks parasite adhesion, indicating the 45-kDa mucin is essential for invasion.
- This mucin represents a promising target for therapeutic intervention against Chagas disease.