In Brief

Development

A clonogenic bone marrow progenitor specific for macrophages and dendritic cells. Fogg, D. K. et al. Science 1 Dec 2005 (doi:10.1126/science.1117729)

Although the origins of macrophages and dendritic cells (DCs) have been well studied, the lineage relationship between these cell types is unclear. Macrophages and DCs belong to the mononuclear-phagocyte system, and it has therefore been suggested that they arise from a common progenitor. To test this directly, Fogg et al. identified a mouse bone-marrow population that expresses both CX₃C-chemokine receptor 1 (CX₃CR1) and KIT but not lineage (Lin). Colonies arising from single CX₃CR1⁺KIT⁺Lin⁻ cells contained macrophages and DCs but not other cell lineages: the presence of macrophage colony-stimulating factor (M-CSF) favoured macrophage development, whereas the presence of granulocyte/macrophage CSF favoured DC development. Moreover, in vivo transfer analysis of fluorescently labelled CX₃CR1⁺KIT⁺Lin⁻ cells indicated that these progenitors could give rise to splenic DCs and other macrophage populations, such as brain microglial cells.

Immune evasion

Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity. Li, X.-D. et al. Proc. Natl Acad. Sci. USA 102, 17717–17722 (2005)

In this study, the authors identify the protein that is targeted by the hepatitis-C-virus-encoded serine protease NS3–NS4A, which enables the virus to establish chronic infection. In response to viral infection, retinoic-acid-induced gene I (RIG-I) recognizes viral double-stranded RNA and interacts with mitochondrial antiviral signalling protein (MAVS; also known as VISA and CARDIF), which triggers the expression of type I interferons (IFNs). However, Li et al. now show that NS3–NS4A colocalizes, binds and cleaves MAVS, resulting in the dislocation of MAVS from the mitochondria, thereby suppressing type I IFN expression. The cleavage site of MAVS requires Cys508, because mutation of this residue renders MAVS resistant to cleavage by NS3–NS4A. So, blocking of this host–pathogen interaction could be applied to the prevention or treatment of hepatitis C virus.

B-cell responses

Cell surface recycling of internalized antigen permits dendritic cell priming of B cells. Bergtold, A. et al. Immunity 23, 503–514 (2005)

The ability of dendritic cells (DCs) to prime naive T cells is undisputed; by contrast, their ability to prime B cells is less well understood. In this study, Bergtold et al. show that DCs can endocytose antigen through the inhibitory Fc receptor for IgG (FcγRIIB) and recycle it to the cell surface for presentation to B cells. In contrast to antigen that is internalized by activating FcγRs, FcγRIIB-endocytosed antigen does not enter degradative vesicular compartments but instead is directed to recycling endosomes and reaches the cell surface as native antigen. Mice that were immunized with IgG-opsonized T-cell-independent antigen had increased humoral responses; this was not seen in FcγRIIB-deficient mice, indicating a mechanism of FcγRIIB-dependent antibody enhancement of T-cell-independent humoral responses in vivo.