title: Differential proteomics reveals age-dependent liver oxidative costs of innate immune activation in mice.
abstract: Individual response to an immune challenge results from the optimization of a trade-off between benefits and costs of immune cell activation. Age-related immune disorders may have several mechanistic bases, from immune cell defects to chronic pro-inflammatory status and oxidative imbalance, but we are still lacking experimental data showing the relative importance of each of these mechanisms. Using a proteomic approach and subsequent biochemical validations of proteomics-derived hypotheses, we found age-dependent regulations in the liver of 3-months and 1-year old-mice in response to an acute innate immune activation. Old mice presented a chronic up-regulation of several proteins involved in pathways related to oxidative stress control. Interestingly, these pathways were weakly affected by the innate immune activation in old compared to young individuals. In addition, old mice suffered from lower glutathione-S-transferase activity and from higher oxidative damage at the end of the experiment, thus suggesting that they paid a higher immune-related cost than young individuals. On the whole, our data showed that a substantial fraction of the liver costs elicited by an activation of the innate immune response is effectively related to oxidative stress, and that ageing impairs the capacity of old individuals to control it.
  
  
  CONCLUSIONS
  Our paper tackles the open question of the cost of mounting an innate immune response. Evolutionary biologists are familiar since a long time with the concept of trade-offs among key traits of an organism, trade-offs that shape life history trajectories of species and individuals, ultimately in terms of reproduction and survival. On the other hand, medicine and molecular biologists study the intimate mechanisms of immune senescence and underline that oxidative imbalance is probably playing a key role in the progressive loss of immune function with age. This paper merges the two fields by exploring the nature of the cellular pathways that are mainly affected by age when the innate immunity is triggered. To this purpose, a proteomic approach was used to explore liver protein profiles and provide for the first time convincing data supporting the idea that oxidative stress constitutes a cost of innate immune response in old mice, possibly contributing to senescence. Proteomics-derived hypotheses were furthermore validated using biochemical assays. This paper therefore illustrates the added value of using proteomics to answer evolutionary biology questions, and opens a promising way to study the inter-specific variability in the rates of immune-senescence.
authors.affiliation: Institut Pluridisciplinaire Hubert Curien, Département Sciences Analytiques, CNRS UMR7178, 25 rue Becquerel, 67087 Strasbourg Cedex 2, France; Université de Strasbourg, 4 rue Blaise Pascal, F-67081 Strasbourg Cedex, France.
authors.forename: Marine I
authors.initials: MI
authors.lastname: Plumel
authors.affiliation: Institut Pluridisciplinaire Hubert Curien, Département Sciences Analytiques, CNRS UMR7178, 25 rue Becquerel, 67087 Strasbourg Cedex 2, France; Université de Strasbourg, 4 rue Blaise Pascal, F-67081 Strasbourg Cedex, France.
authors.forename: Margaux
authors.initials: M
authors.lastname: Benhaim-Delarbre
authors.affiliation: Institut Pluridisciplinaire Hubert Curien, Département Sciences Analytiques, CNRS UMR7178, 25 rue Becquerel, 67087 Strasbourg Cedex 2, France; Université de Strasbourg, 4 rue Blaise Pascal, F-67081 Strasbourg Cedex, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Rompais
authors.affiliation: Institut Pluridisciplinaire Hubert Curien, Département Sciences Analytiques, CNRS UMR7178, 25 rue Becquerel, 67087 Strasbourg Cedex 2, France; Université de Strasbourg, 4 rue Blaise Pascal, F-67081 Strasbourg Cedex, France.
authors.forename: Danièle
authors.initials: D
authors.lastname: Thiersé
authors.affiliation: Biogéosciences, CNRS UMR6282, Université de Bourgogne, 6 boulevard Gabriel, F-21000 Dijon, France.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Sorci
authors.affiliation: Institut Pluridisciplinaire Hubert Curien, Département Sciences Analytiques, CNRS UMR7178, 25 rue Becquerel, 67087 Strasbourg Cedex 2, France; Université de Strasbourg, 4 rue Blaise Pascal, F-67081 Strasbourg Cedex, France.
authors.forename: Alain
authors.initials: A
authors.lastname: van Dorsselaer
authors.affiliation: Institut Pluridisciplinaire Hubert Curien, Département d'Ecologie, Physiologie et Ethologie, CNRS UMR7178, 23 rue Becquerel, 67087 Strasbourg Cedex 2, France; Université de Strasbourg, 4 rue Blaise Pascal, F-67081 Strasbourg Cedex, France.
authors.forename: François
authors.initials: F
authors.lastname: Criscuolo
authors.affiliation: Institut Pluridisciplinaire Hubert Curien, Département Sciences Analytiques, CNRS UMR7178, 25 rue Becquerel, 67087 Strasbourg Cedex 2, France; Université de Strasbourg, 4 rue Blaise Pascal, F-67081 Strasbourg Cedex, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bertile
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D007113:Immunity, Innate / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D040901:Proteomics
keywords: Ageing; Immunosenescence; Liver; Mice; Oxidative stress; Proteomics