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New frontiers in immunology
Workshop on The Road Ahead: Future Directions in Fundamental and Clinical Immunology
Bruce Beutler1+ & Jean-Laurent Casanova2++

The Scripps Research Institute, La Jolla, California, USA, and 2University of Paris René Descartes, Necker Medical School, Paris, France

The EMBO workshop on ‘The Road Ahead: Future Directions inFundamental and Clinical Immunology’ was held at the Centre d’Immunologie de Marseille Luminy in France between 13 and 15 January 2005, and was organized by B. Malissen, J.-P. Gorvel, E. Vivier and J. Ewbank.

immunologists also feel that a central question revolves around the molecular events that initiate or inhibit T-cell activation, and those with a practical bent point to autoimmune diseases asa key challenge. These topics were all discussed at the EMBO workshop ‘The Road Ahead: Future Directions in Fundamental and Clinical Immunology’.

Immunity to infection across the animal kingdom
There are nearly ubiquitous microbes but no ‘universal’ pathogens. Even the most dreaded human pathogens are innocuous in one species or another, and usually in most. For example, human immunodeficiencyvirus (HIV) is not a pathogen of mice. However, adaptive immunity is a relative constant: the same type of combinatorial system for antigen recognition exists in all mammals. This in itself suggests that inherited disease resistance, or innate immunity, can protect the host against any microbe, and may be the more powerful of the two systems (Beutler & Rietschel, 2003; Casanova et al, 2002).Classical genetics has yielded much progress in understanding innate immunity; we finally know what most of the innate receptors are and how they signal. Model organisms have played a large part in this story. Caenorhabditis elegans, Drosophila melanogaster, and even plants such as Arabidopsis thaliana, each have mechanisms for resisting infection. J. Ewbank (Marseille, France) discussed specificityin C. elegans innate immunity. Here, it seems, innate immunity is discharged by a Toll-like receptor (TLR): much like the situation in Drosophila and mammals. However, the single TLR of C. elegans is expressed in neurons and confers avoidance behaviour, causing the worms to eschew the pathogenic microbe Serratia marcescens (Schulenburg et al, 2004). One does not normally expect host defence to bemediated neurologically, but in this case it seems to be. B. Lemaitre (Gif-sur-Yvette, France) expanded on innate immune sensing in Drosophila spp. and discussed how flies both sense bacterial infection and discriminate between Gram-negative and Gram-positive bacteria (Vodovar et al, 2004). He pointed out that Drosophila can serve both as an innate immune model and as part of a host–pathogeninteraction model. As in the case of C. elegans, the identification of ‘natural’ fly pathogens is a difficult problem. Proceeding from the observations made in the wild type, two microbes (the Ecc15 strain of Erwinia carotovora carotovora and the

Keywords: immunity; infection; tolerance; auto-immunity
EMBO reports (2005) 6, 620–623.doi:10.1038/sj.embor.7400457

In science, asking the right questions may be more difficult than finding the right answers. Asking may amount to a feat of invention that requires more imagination than any other step in the scientific process. What are the main questions confronting immunologists? Immunologists have always attempted to elucidate the mechanisms of microbial pathogenesis and immunity toinfection. Adaptive
1 Department of Immunology, IMM-31, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA 2 Laboratory of Human Genetics of Infectious Diseases, University of Paris René Descartes—INSERM U550, Necker Medical School, 156 Rue de Vaugirard, 75015 Paris, France + Corresponding author. Tel: +1 858 784 8610; Fax: +1 858 784 8444; E-mail:...
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