Background: The first identified susceptibility gene for Crohn's disease, NOD2, acts as a sensor for the bacterial-wall peptidoglycan fragment muramyl dipeptide (MDP) and activates the transcription factor nuclear factor-kappa B (NF-kappa B). Upon NF-kappa B activation, intestinal macrophages (IMACs) induce expression of macrophage inflammatory protein (MIP)-3 alpha to attract memory T lymphocytes. We therefore investigated the influence of NOD2 ligation of IMAC differentiation and functional MIP-3 alpha induction. Methods: Human embryonal kidney HEK293 cells were transfected with NOD2 wildtype (NOD2(WT)) and the NOD2 SNP13 variant (NOD2(L1007fsinsC)) and stimulated with MDP. Recruitment of CD45R0(+) and Th17 cells was determined by immunohistochemistry. Results: Endogenous NOD2 stimulation was followed by a dose-dependent increase in MIP-3 alpha secretion in MONO-MAC-6 (MM6) cells. MIP-3 alpha mRNA was also significantly (* p < 0.05) induced in HEK293 transfected with NOD2(WT) via MDP ligation. In vivo cell-cell contacts between IMACs and CD45R0(+) memory T cells as well as recruitment of Th17 cells in patients of NOD2 variants were unchanged as compared to wild-type patients. Conclusion: Our data demonstrate a dose-dependent increase in MIP-3 alpha secretion in the human myeloid cell line MM6 upon MDP. However, MIP-3 alpha-driven recruitment of Th17 cells or CD45R0(+) memory T lymphocytes is not affected in patients carrying heterozygous NOD2 variants. Copyright (C) 2012 S. Karger AG, Basel