Toxoplasma gondii profilin does not stimulate an innate immune response through bovine or human TLR5

Area of Science:

• Immunology
• Parasitology
• Molecular Biology

Background:

• Toxoplasma gondii (T. gondii) causes widespread human infections, with its profilin (TgPr) protein crucial for parasite motility and invasion.
• Murine Toll-like receptors (TLRs) are known to bind TgPr, and human TLR5 has been reported to recognize TgPr and bacterial flagellin.
• Understanding innate immune recognition of T. gondii in livestock is limited, despite its prevalence in farm animals.

Purpose of the Study:

• To investigate if bovine and porcine TLR5 can be stimulated by T. gondii profilin (TgPr), similar to human TLR5.
• To assess the innate immune recognition of TgPr in non-murine systems, specifically focusing on TLR5 activation.

Main Methods:

• Utilized reporter cell lines expressing full-length human, bovine, and porcine TLR5.
• Stimulated reporter cells and primary human peripheral blood mononuclear cells (PBMCs) and CD14+ monocytes with TgPr and flagellin.
• Measured IL-6 secretion as an indicator of immune response.
• Exposed RAW cells, known to express TLR11, to TgPr.

Main Results:

• Human and bovine TLR5-transfected cells responded to flagellin but not to TgPr.
• TgPr did not induce IL-6 secretion in human PBMCs or CD14+ monocytes.
• RAW cells (TLR11 expressing) showed a slight increase in IL-6 response upon TgPr exposure.

Conclusions:

• The study casts doubt on TgPr being a specific ligand for human and bovine TLR5.
• The immunogenic properties of TgPr remain uncharacterized in humans and livestock outside the murine system.
• Further research is needed to elucidate the innate immune recognition mechanisms for T. gondii profilin in non-murine species.