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Blood, 15 December 2006, Vol. 108, No. 13, pp. 3959. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ferrara, J. L. M. Search for Related Content PubMed Articles by Ferrara, J. L. M. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Comment on Bartz et al, page 4102 Career choices of monocytes in dangerous times James L. M. Ferrara UNIVERSITY OF MICHIGAN Monocytes can differentiate into a number of end-stage effector cells. In this issue of Blood, Bartz and colleagues show that danger signals via toll-like receptors (TLRs) drive monocytes to differentiate into macrophages and prevent them from becoming dendritic cells, through the up-regulation of suppressor of cytokine signaling (SOCS) proteins. Cells of the innate immune system recognize infectious organisms through pattern recognition receptors that include members of the TLR family. Many hematopoietic progenitors, including hematopoietic stem cells, express TLRs, and their ligation can direct the differentiation of these cells into various lineages.1 As precursor cells in the innate immune system, monocytes are of particular interest in this regard: they can differentiate into phagocytic macrophages, an important immediate defense against bacteria, or into dendritic cells (DCs), the most potent professional antigen-presenting cells that orchestrate adaptive immune responses. This switch may play an important role in host defense. For example, monocytes from patients with progressive, systemic leprosy become primarily macrophages, whereas monocytes from patients with limited disease become DCs as well as macrophages.2 Cytokines, particularly granulocyte-macrophage colony-stimulating factor (GM-CSF), are key drivers of the developmental switch of monocytes into DCs. The study by Bartz and colleagues offers mechanistic insights into this switch, showing that TLR signals override GM-CSF signaling and prevent DC maturation. This switch appears to operate through the induction of SOCS family proteins, which are increased after TLR ligation. Overexpression of SOCS1 also blocks GM-CSF signaling and prevents DC maturation. There are a few important caveats to these conclusions. This work was performed in vitro, and there is no direct evidence yet that this mechanism pertains in vivo. Forced overexpression of SOCS proteins may have nonspecific effects that could limit the interpretation of these results. But the findings suggest a mechanism of how danger signals3 influence the functional development of immune cells for short-term versus long-term defense. During an ongoing infection, microbial products alert the immune system to immediate danger, increasing the number of macrophages that can phagocytose the invaders, at the expense of DCs. This mechanism could help explain why patients with sepsis are immunodeficient, and may suggest differential strategies for modulating or amplifying immune responses depending on whether the immune system is responding to an active infection or preparing for a future one. The author declares no competing financial interests. References Nagai Y, Garrett KP, Ohta S, et al. Toll-like receptors on hematopoietic progenitor cells stimulate innate immune system replenishment. Immunity. 2006;24: 801-812.[CrossRef][Medline] [Order article via Infotrieve] Krutzik SR, Tan B, Li H, et al. TLR activation triggers the rapid differentiation of monocytes into macrophages and dendritic cells. Nat Med. 2005;11: 653-660.[CrossRef][Medline] [Order article via Infotrieve] Matzinger P. The danger model: a renewed sense of self. Science. 2002;296: 301-305.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Involvement of suppressors of cytokine signaling in toll-like receptor–mediated block of dendritic cell differentiation Holger Bartz, Nicole M. Avalos, Andrea Baetz, Klaus Heeg, and Alexander H. Dalpke Blood 2006 108: 4102-4108. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ferrara, J. L. M. Search for Related Content PubMed Articles by Ferrara, J. L. M. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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