MD-2 expression is not required for cell surface targeting of Toll-like receptor 4 (TLR4)

The cell surface receptor complex formed by TLR4 and myeloid differentiation 2 (MD‐2) is engaged when cells are exposed to LPS. Recent studies suggested that surface localization of functional mouse TLR4 (mTLR4) depends on the simultaneous expression of MD‐2. As we did not observe a similar requirement, we conducted a comparative study of human TLR4 and mTLR4 surface expression in immune cells derived from the MD‐2 knockout mouse and LPS‐responsive cell lines and in cells that ectopically express TLR4. Our results indicate that in the human and mouse models, neither TLR4 function nor TLR4 surface targeting requires MD‐2 coexpression. Accordingly, we report on one human cell line, which constitutively expresses functional TLR4 on the cell surface in the absence of MD‐2 expression.