Recruitment of distinct immune cell populations to the lung after intratracheal TLR4 signaling activation by two different stimulations

The toll-like receptor 4 (TLR4)-mediated immune response is considered as one of the triggers of acute respiratory distress syndrome. The agonistic monoclonal antibody UT12 specific for the TLR4/MD2 complex induces immune activation in a manner distinct from lipopolysaccharide (LPS). In order to compare the effects of this differential TLR4 signaling activation, we examined immune cell recruitment to the lung following intratracheal inoculation with UT12 and LPS in mice. The increase in pulmonary neutrophils was much higher after LPS treatment compared with UT12 treatment, while CD11bhiCD11＋cells increased to similar levels following both treatments. These changes were MyD88-dependent and TRIF-independent. These differential effects on immune cell recruitment to the lung suggest distinct underlying mechanisms in response to TLR4 stimulation. These findings further indicate that TLR signaling can lead to different outcomes depending on the ligand and activation pathway, which may relate to the complex pathogenesis of inflammatory lung diseases