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The Drosophila, or
vinegar fly, is a model of choice for examining the molecular mechanisms
of the immunity of invertebrates. The results obtained by Jules Hoffmann
and his team at the "Réponse immunitaire et développement
chez les insectes" Laboratory (Insect Immune Response and Development
Laboratory, CNRS – Strasbourg), published in the December 13 issue
of Nature, elucidate the role of microbial peptides (the peptidoglycan
recognition protein, or PGRP) in the immune response of insects. The presence
of genes homologous to the PGRP in vertebrates shows similarities in the
immune responses developed within the animal kingdom throughout its evolutionary
history.
Certain species of micro-organisms
are pathogenic and can cause serious biological dysfunctions in the infected
hosts, and in some cases, lead to the host's death. In order for a certain
harmony to continue in the living world, a balance must be struck between
the organisms that seek to protect themselves from infectious agents and
the microbes that attempt to bypass the hosts' defenses. Animal and plant
species must deal with the same major groups of micro-organisms (bacteria,
viruses, fungi, yeasts, etc.), and over the course of evolution, each
species has developed its own system of defense. Although the molecular
mechanisms used are different, the same objectives must be attained: the
contaminated organism must first identify the aggressor and then neutralize
it.
Invertebrates lack the adaptive immune system of vertebrates that gives
rise to, among other things, the production of antibodies. Invertebrates
fight infectious agents only with their innate immune system, producing,
in particular, antimicrobial peptides. The synthesis of these molecules
occurs before the micro-organism is identified. The molecules involved
in this recognition, in both vertebrates and invertebrates, are not yet
well understood. The genetics of the Drosophila have proved to
be a powerful tool in improving our knowledge about these molecules.
The work of Julien Royet's team at the Insect Immune Response and Development
Laboratory has made it possible to isolate a Drosophila mutant
that is incapable of recognizing a certain type of pathogenic bacteria:
Gram-positive bacteria. Drosophila that carry the mutation rapidly
succumb to Gram-positive infections. Isolating this mutant line enabled
the scientists to reveal the inactivated protein involved in the recognition
process. In vitro experiments have demonstrated that this PGRP protein
(the peptidoglycan recognition protein) can bind to peptidoglycan, a major
peptide and sucrose component of the cell wall that surrounds Gram-positive
bacteria. Study of the defense mechanism of mutants when confronted with
Gram-negative bacteria suggests that the host uses different molecules
to detect each of the families of micro-organisms.
The presence of PGRP proteins in the human genome suggests that at least
one part of the recognition stage has been preserved during the evolution
of mankind. Further work on the Drosophila could also enlighten
us on how the innate aspects of our own immune system function.
Reference:
T. Michel, J.-M. Reichhart, J. Hoffmann and J. Royet. Drosophila
Toll is activated by Gram-positive bacteria through a circulating peptidoglycan
recognition protein. Nature, vol 414, (2001).
Researcher
contact:
Julien Royet
Tel: + 33 3 88 41 70 17
E-mail: J.Royet@ibmc.u-strasbg.fr
CNRS Life Sciences Department contact:
Marie-Pascale Corneloup-Brossollet
Tel: + 33 1 44 96 46 48
E-mail: marie.corneloup@cnrs-dir.fr
Press contact
:
Martine Hasler
Tel : +33 1 44 96 46 35
E-mail : martine.hasler@cnrs-dir.fr
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