Figure 2.

Modulation of cells of the innate and adaptive immune system by LF contributes to host defense. (a) In early phases of the immune response to invading pathogens, LF released from neutrophil granules has an immunostimulatory role because of its function as an alarmin to mediate immune cell recruitment from the bloodstream to the affected tissue (1) and by activation of myeloid cells—macrophages (2) and DCs (3) in particular. These LF actions might be in part related to its ability to serve as a PAMP carrier. Lastly, by promoting DC maturation (4), LF has a positive influence on functions of the adaptive immune system by activating, for instance, T cells (5). (b) In contrast, in chronic infection or inflammation (e.g., in allergic inflammation), LF exerts immunomodulatory functions and, therefore, protective effects via several mechanisms. LF efficiently counteracts the excessive proinflammatory responses of macrophages triggered by PAMPs (6) and shrinks neutrophil extracellular traps (7). LF also efficiently scavenges free ferric iron, thereby blocking deleterious ROS production (8). In allergy, LF is known to modulate DC functions (9), thereby skewing the immune response from the harmful Th2 to the protective Th1 type (10) that is accompanied by reduced production of allergen-specific IgE antibodies by B cells.