Le langage moléculaire des parasites

Abstract

The host-parasite relationship is governed by a complex network of interactions resulting in a subtle balance between host-defense mechanisms and survival strategies mounted by parasites. In response to the selection pressures imposed by adaptation requirements, both parasites and hosts have had to make significant genetic adjustments. Apart from neo-Darwinism selection, several additional mechanisms can be invoked to account for such adjustments. Molecular mimicry, a concept developed in the early 1960's, is based on several reports of the presence of host antigens on or in parasites. For instance, schistosomes share antigenic determinants both with their intermediate and definitive hosts. The reduction of antigenic disparity between host and parasite could contribute to a state of host tolerance which allows parasite survival. In some cases, it is likely that host-like molecules identified in parasites were passively acquired, but evidence of the genetic capacity of parasites to produce host-like molecules have now been put forward. Such homology represents either conservation during the evolution of metazoan animals or more recent adaptative change consecutive to selective pressure. Recent work on the characterization of several invertebrate tropomyosins indicate that in this case mimicry is superimposed upon molecular conservation. The direct incorporation of host genetic material in the parasite genome represents another alternative. Likely candidates for effecting transfer of genetic information between hosts and parasites are the retroviruses and such exchange opens up the possibility of more rapid evolution. Capture of host signals: as a consequence of their ability to acquire host molecules, parasites use host signals for their growth and differentiation. IL-2, IL-3 and GM-CSF are growth factors for different species of Leishmania while TNF-α is a powerful stimulus for the reproduction of schistosomes. The use of host signals such as cytokines, growth factors and neuropeptides by parasites implies the presence of binding structures on their surface. Parasites can also exert a direct regulatory effect on host cytokine production and these recent reports bring new arguments in favor of a co-evolution of parasites and host cytokine responses. Lures of communication: one of the most fascinating parasite strategies to avoid host immune response leads in the release of immunomodulating substances. Immunosuppressive substances or polyclonal activators have been described in several models. Unfortunately, most of these factors are poorly characterised at the molecular level. Another tactic has been developed by helminth parasites, that acts by modulating immune effector mechanisms. Integrated language of parasites: during the last years, evidence has been presented that the nervous and particularly neuroendocrine system communicates with the immune system through a bidirectional dialogue calling out cytokines, biogenic amines and neuropeptides. Considering the immunomodulatory properties of proopiomelanocortine (POMC)-derived peptides and their phylogenetic conservation, we have postulated their existence in schistosomes. In fact, schistosomes produce significant quantities of β-endorphin, adrenocorticotropin and melanocyte stimulating hormone which have immunosuppressive properties on the immune system of both intermediate and definitive hosts. The demonstration of a complete POMC system in parasites supports the hypothesis of a common origin of messengers of cellular communications in vertebrate and invertebrates. It remains to determine the effects of such common signals both on the physiology of the parasite and of the host. As shown by examples mentioned here, parasite language resulting from the co-evolution of parasites and their hosts represents by its diversity and fitness a remarkable model of cellular sociology.