RAPID COMMUNICATION: TLR4 expressed but with reduced functionality on equine B lymphocytes

Area of Science:

• Immunology
• Veterinary Medicine
• Cell Biology

Background:

• Mammalian species exhibit varying susceptibility to endotoxemia, a condition caused by lipopolysaccharide (LPS) from gram-negative bacteria.
• Toll-like receptor 4 (TLR4) mediates LPS response and is found on immune cells like B lymphocytes.
• Horses are highly sensitive to endotoxemia, often complicating colic, but TLR4 expression and function on their B lymphocytes remain unknown.

Purpose of the Study:

• To investigate the expression and function of Toll-like receptor 4 (TLR4) on equine B lymphocytes.
• To compare the LPS responsiveness of horse B lymphocytes with that of mouse B lymphocytes.

Main Methods:

• Peripheral blood mononuclear cells were collected from six horses.
• Flow cytometry was used to analyze TLR4 expression on B lymphocytes.
• In vitro stimulation with LPS was performed to assess B lymphocyte proliferation and gene expression.

Main Results:

• TLR4 was expressed on equine B lymphocytes, but LPS stimulation did not alter its expression.
• Equine B lymphocytes did not proliferate in response to LPS in vitro, unlike mouse B lymphocytes.
• No significant differences were observed in key TLR4 signaling pathway genes (TLR4, IL-10, IL-6, IFNβ, TNFα) between stimulated and unstimulated horse lymphocytes.

Conclusions:

• Equine B lymphocytes express TLR4 but demonstrate minimal in vitro responsiveness to LPS.
• This limited responsiveness mirrors findings in human B lymphocytes, which are also less sensitive to LPS.
• The study suggests a potential correlation between equine B lymphocyte TLR4 expression/function and their high susceptibility to endotoxemia.