Related Experiment Video
Updated: May 29, 2026
Murine Model of Epicutaneously-Induced Immunomodulation
Published on: June 24, 2025
Receptor usage by the Acanthocheilonema viteae-derived immunomodulator, ES-62
William Harnett1, Helen S Goodridge, Janet M Allen
1Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK. w.harnett@strath.ac.uk
Insights
ES-62, an immunomodulatory glycoprotein, binds to different proteins on various immune cells. Phosphatidylcholine (PC) is key for this binding, and Toll-like receptor 4 (TLR4) influences ES-62 internalization in macrophages.
Area of Science:
- Immunology
- Parasitology
- Molecular Biology
Background:
- ES-62 is an immunomodulatory glycoprotein from Acanthocheilonema viteae.
- Previous studies indicated Toll-like receptor 4 (TLR4) dependence for ES-62 effects on macrophages and dendritic cells.
- Potential for ES-62 to interact with diverse cell surface proteins, leading to varied receptor usage.
Purpose of the Study:
- To identify proteins interacting with ES-62 across different immune cell types.
- To investigate the role of phosphatidylcholine (PC) in ES-62 binding.
- To determine the involvement of TLR4 in ES-62 internalization.
Main Methods:
- Protein identification by molecular weight after ES-62 interaction.
- Assessment of PC's effect on ES-62 binding.
- Analysis of ES-62 internalization in the presence or absence of TLR4.
Main Results:
- Lymphocytes show ES-62 interaction with proteins at ~135 kDa and ~82 kDa.
- U937 monocytes exhibit ES-62 binding to an ~82 kDa protein.
- PC blocked ES-62 binding to B cells and U937 cells, highlighting PC's role.
- ES-62 internalization occurred in macrophages and B cells; TLR4 absence blocked it only in macrophages.
Conclusions:
- ES-62 exhibits differential receptor usage across immune cell types.
- Phosphatidylcholine is crucial for ES-62-mediated cell interactions.
- TLR4 plays a cell-specific role in ES-62 internalization.
Abstract:
ES-62 is an immunomodulatory phosphorylcholine (PC)-containing glycoprotein secreted by the rodent filarial nematode Acanthocheilonema viteae. Previously, the use of knockout mice has revealed the effects of ES-62 on macrophages and dendritic cells to be dependent on TLR4. However, it is possible that ES-62 may interact with additional proteins on the surfaces of target cells and hence that cells may vary with respect to receptor usage. In this study, we identified by molecular weight, proteins that interact with ES-62 and found differences amongst the immune system cells studied. Thus, whereas lymphocytes appear to have two major interacting proteins of ∼135 and ∼82 kDa, U937 monocytes only contain an ES-62-binding protein of the latter molecular weight. Binding to the proteins on B cells and U937 cells was blocked by PC, suggesting a critical role for this ES-62 moiety in facilitating interaction. Finally, ES-62 binding is followed by internalization in both macrophages and B cells but only in the former was absence of TLR4 found to block internalization. These findings are consistent with differences in receptor usage by ES-62 amongst different cell-types.
