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 distresssyndrome. The agonistic monoclonal antibody UT12 specific for the TLR4/MD2 complex induces immune activation in a mannerdistinct from lipopolysaccharide (LPS). In order to compare the effects of this differential TLR4 signaling activation, we examinedimmune cell recruitment to the lung following intratracheal inoculation with UT12 and LPS in mice. The increase in pulmonaryneutrophils was much higher after LPS treatment compared with UT12 treatment, while CD11bhiCD11＋cells increased to similarlevels following both treatments. These changes were MyD88-dependent and TRIF-independent. These differential effects onimmune cell recruitment to the lung suggest distinct underlying mechanisms in response to TLR4 stimulation. These findingsfurther indicate that TLR signaling can lead to different outcomes depending on the ligand and activation pathway, which mayrelate to the complex pathogenesis of inflammatory lung diseases