Uptake and nuclear translocation of lactoferrin by porcine monocytes: impact of iron binding, protease activity, and monocyte activation.

Lactoferrin (LF) is a glycoprotein found in neutrophils, milk, and various mammalian secretions that plays a crucial role in host defense by modulating the immune response. Previous studies have shown that LF is taken up by human monocytes and can be present in their nucleus. However, it is unclear whether the iron saturation levels or the protease activity of LF are involved in this uptake and nuclear translocation. In addition, the activation of monocytes might influence these processes. The present study investigated the uptake and nuclear translocation of bovine LF (bLF) and porcine LF (pLF) in porcine blood-derived monocytes and how this affects monocyte function. Both bLF and pLF were internalized by porcine monocytes. Their uptake was not affected by increased iron saturation levels or by inactivation of the proteolytic activity of LF. Similarly, LPS-induced activation of monocytes did not affect LF internalization. We further investigated whether bLF could modulate LPS-induced cytokine responses by monocytes. Across all tested LPS serotypes and concentrations, bLF failed to decrease the LPS-induced TNF-α secretion by porcine monocytes. Besides internalization, we found that bLF and pLF translocated to the nucleus in a subset of porcine monocytes. This nuclear translocation was not affected by the iron saturation level and proteolytic activity of LF, nor by LPS-induced monocyte activation. Together, these findings further deepen our understanding of LF's interaction with porcine innate immune cells and provide insights into its immunomodulatory properties.