Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2

Speaker: 張振田                    Time: 14:00~15:00 4/12/2006

Commentator:                       Place: Room 601

Abstract:

Monocytes, a heterogeneous leukocyte population, are generated from bone marrow, and then released into circulation.  When recruited into tissue, monocytes can transform to macrophages, dendritic cells and play an important role in innate and adaptive immune responses.  However, the molecular mechanism regulating proliferation and mobilization of monocytes in response to infection and inflammation is not well understood.  Previous data showed that progenitor stem cells are actively retained in the bone marrow via chemokine –mediated signals , meanwhile, CCR2 deficiency mice have enhanced susceptibility to Listeria monocytogensinfection due to lacking tumor necrosis factor (TNF)- and inducible nitric oxide synthase (iNOS)- producing dendritic cells (called TipDCs) in the spleen.  These studies indicate that chemokine receptors and their ligands may have a major role in monocyte trafficking during bacterial infection.  In this study, using L. monocytogensinfection model and monocyte surface makers, the authors demonstrated that CCR2-mediated signals were required for the emigration of Ly6C^hiTipDC precursors from the bone marrow into the circulation.  However, the adoptive transfer experiment showed that migration of TipDCs from the bloodstream to infected spleen did not required CCR2.  Further analysis of uninfected mice suggested that CCR2 signaling contributes to monocyte homeostasis even in noninflammatory conditions.  These results establish the involvement of CCR2 in promoting monocyte emigration from the bone marrow and provide a novel treatment strategy for monocyte-related diseases.

References:

1. Gordon,S. and Taylor,P.R. (2005). Monocyte and macrophage heterogeneity. Nat. Rev. Immunol. 5, 953-964.

2. Serbina,N.V. and Pamer,E.G. (2006). Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat. Immunol. 7, 311-317.