Background: Liver is exposed to bacterial components related to intestinal permeability.NOD1, a bacterial receptor, appears to regulate the crosstalk between innate and adaptive immunity and the functions of polymorphonuclear neutrophils (PMN) in intestinal diseases.No data are available concerning the role of NOD1 in PMN related liver diseases.Aim: To explore the regulatory role of NOD1 in the PMN-induced liver injury.Methods: Livers taken from Nod1 +/ + and Nod1 -/ -mice challenged with CCl 4 were examined; main functions of PMN isolated from Nod1 +/ + and Nod1 -/ -mice were studied.Migration tests were performed in Boyden chambers using chemoattractants.Phagocytosis capacity was tested using the Phagotest ® ; we studied the main inflammatory pathways in PMN and CD11b expression on PMN surface by FACS analysis.Results: We observed that NOD1 was expressed in hepatocytes and PMN at mRNA and protein levels.In PMN-mediated injury models in mice, we showed that: After CCl 4 exposure, livers of Nod1 -/ -mice disclosed more than 50% lower PMN infiltration within necrotic areas compared to Nod1 +/ + .A lower PMN infiltration was also observed in Nod1 -/ -mice using a thioglycolate-mediated peritonitis model; The lack of difference in the liver expression of mRNA chemokines between Nod1 -/ -and control mice.There were no constitutional defects in blood formula or in granuloblasts isolated from bone marrow in Nod1 -/ -mice.Taken together these results suggested an impaired PMN recruitment.Then, in ex-vivo studies, we focused on PMN functions: PMN isolated from Nod1 -/ - mice displayed a 90% decrease in migration capacity compared to the Nod1 +/ + PMN; FK565, a potent ligand of NOD1, increased significantly human PMN migration; Phagocytosis capacity of Nod1 -/ -neutrophils was decreased by more than 50% compared to Nod1 +/ + .In terms of mechanistic insights: upon FK565 and fMLP stimulation, p38, JNK and NFkB activations were altered in Nod1 -/ -PMN; expression of CD11b on the Nod1 -/ -PMN surface was significantly decreased compared to Nod1 +/ + .Conclusions: NOD1 is involved in the ability of PMN to migrate in the liver.In terms of mechanisms, the defect of NOD1 leads to altered functional activities of PMN.NOD1 may be an interesting target to regulate PMN-related liver injury.