Trends in Immunology
Research updateMacrophage signaling, apoptosis, lectins and leukocyte trafficking
Section snippets
Signal transduction in macrophages
In the first session, L. O'Neill (Dublin, Ireland) reviewed the signaling pathways activated by interleukin-1 (IL-1) and Toll-like receptors (TLRs), indicating that TLR-domain-containing receptors are an important switch for innate immunity and inflammation. He presented data on a novel TLR-domain-containing protein, termed MyD88-adapter-like (Mal), which forms a heterodimer with MyD88 and recruits IL-1-receptor-associated kinase 2 (IRAK-2) selectively. Thus, Mal appears to play a role
Macrophages and apoptosis
In the second session, it was noted that cells undergoing apoptosis are eliminated rapidly and selectively by phagocytes, and evidence demonstrating the importance of this event has accumulated. Immediate issues to be solved include the mechanism of phagocytic recognition of target apoptotic cells and the physiological role of this phenomenon. In this session, six speakers presented their recent observations. V. Fadok (Denver, CO, USA) emphasized that a phosphatidylserine (PS) receptor she
Lectins and the recognition of carbohydrate
In the third session, five presentations focused on the regulated expression and functional relevance of lectins, carbohydrate ligands and glycosyltransferases, implying that the interaction between endogenous lectins and their carbohydrate ligands is involved potentially in the uptake of antigen, cell trafficking and intercellular communication in the immune system. S. Saeland (Schering Plough, France) showed the molecular structures and biological functions of two lectins, a
Chemokines in the dynamics of leukocyte trafficking
In the final session, A. Lanzavecchia (Bellinzona, Switzerland) presented an outline of T-lymphocyte activation, differentiation and migration in several model systems. Of note, human memory T cells comprise two distinct populations: nonpolarized CC-chemokine receptor 7 (CCR7)+ central memory cells and polarized [T helper 1 (Th1) or Th2] CCR7− effector memory cells. R. Forster (Erlangen, Germany) presented data suggesting that chemokines and their receptors are involved essentially in the
Key outcomes of the meeting
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TLRs are phylogenetically conserved receptors that are essential for the recognition of pathogens. Different TLRs recognize different microbial cell-wall components (e.g. TLR2, TLR4 and TLR 9 recognize peptide-glycans, LPS and CpG DNA, respectively).
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Other molecules that interact with TLR4, such as Mal, MyD88, MD1 and MD2, are also essential for signaling by LPS.
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PS receptors and ABC1 transporters play a key role in the elimination of apoptotic cells by macrophages and the resulting inflammatory
Acknowledgements
The meeting was organized by T.K. We thank Y. Kobayashi, Y. Nakanishi, N. Higashi and T. Irimura for preparing short summaries of each session and L. O'Neill for reviewing the manuscript. Symposium abstracts are available online at http://www.prevent.m.u-tokyo.ac.jp