Towards a liquid self: how time, geography, and life experiences reshape the biological identity.
The conceptualization of immunological self is amongst the most important theories of modern biology, representing a sort of theoretical guideline for experimental immunologists, in order to understand how host constituents are ignored by the immune system (IS). A consistent advancement in this field has been represented by the danger/damage theory and its subsequent refinements, which at present represents the most comprehensive conceptualization of immunological self. Here, we present the new hypothesis of "liquid self," which integrates and extends the danger/damage theory. The main novelty of the liquid self hypothesis lies in the full integration of the immune response mechanisms into the host body's ecosystems, i.e., in adding the temporal, as well as the geographical/evolutionary and environmental, dimensions, which we suggested to call "immunological biography." Our hypothesis takes into account the important biological changes occurring with time (age) in the IS (including immunosenescence and inflammaging), as well as changes in the organismal context related to nutrition, lifestyle, and geography (populations). We argue that such temporal and geographical dimensions impinge upon, and continuously reshape, the antigenicity of physical entities (molecules, cells, bacteria, viruses), making them switching between "self" and "non-self" states in a dynamical, "liquid" fashion. Particular attention is devoted to oral tolerance and gut microbiota, as well as to a new potential source of unexpected self epitopes produced by proteasome splicing. Finally, our framework allows the set up of a variety of testable predictions, the most straightforward suggesting that the immune responses to defined molecules representing potentials antigens will be quantitatively and qualitatively quite different according to the immuno-biographical background of the host.
Interdepartmental Center "Luigi Galvani" for Bioinformatics, Biophysics and Biocomplexity, University of Bologna , Bologna , Italy.
Andrea
A
Grignolio
Centro Interdipartimentale di Ricerca sul Cancro "G. Prodi", University of Bologna , Bologna , Italy ; Institut für Biochemie, Charité - Universitätsmedizin Berlin , Berlin , Germany.
Michele
M
Mishto
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte , Brazil.
Ana Maria Caetano
AM
Faria
Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna , Bologna , Italy.
Paolo
P
Garagnani
Interdepartmental Center "Luigi Galvani" for Bioinformatics, Biophysics and Biocomplexity, University of Bologna , Bologna , Italy ; Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna , Bologna , Italy ; IRCCS of Neurological Science , Bologna , Italy ; Institute of Organic Synthesis and Photoreactivity, National Research Council , Bologna , Italy.
Claudio
C
Franceschi
Institute for Applied Mathematics "M. Picone", National Research Council , Rome , Italy.
Paolo
P
Tieri
N-glycan; antigen presentation; gut microbiota; host–pathogen interaction; non-self; oral tolerance; proteasome splicing; self