Towards a Liquid Self: How Time, Geography, and Life Experiences Reshape the Biological Identity

Andrea Grignolio,Paolo Garagnani,Ana Maria Caetano Faria,Claudio Franceschi,Michele Mishto,Paolo Tieri

doi:10.3389/fimmu.2014.00153

Abstract

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.

Highlights

In its historical development, the conceptualization of the immune self has always suffered of an “ontological obsession” (Box 1)
Our hypothesis takes into account the important biological changes occurring with time in the immune system (IS), as well as changes in the organismal context related to nutrition, lifestyle, and geography.We argue that such temporal and geographical dimensions impinge upon, and continuously reshape, the antigenicity of physical entities, making them switching between “self” and “non-self” states in a dynamical, “liquid” fashion
Self had been focused on physical entities that Burnet identified as B lymphocytes [1, 2] and, later on, Janeway and Matzinger identified as pathogen-associated molecular patterns (PAMPs)

Summary

INTRODUCTION

The conceptualization of the immune self has always suffered of an “ontological obsession” (Box 1). (3, 4) and danger signals (endogenous, non-foreign damage/alarm signaling molecules) [5, 6], respectively (Box 2). While playing a fundamental role in the development of the immunological thinking, and because of its lack of sufficient explanatory power of emergent phenomena such as inflammatory and autoimmune diseases [36], the concept of immunological self has nowadays revealed its main limits in excluding the host’s spatial (i.e., geographical and environmental) and temporal (phyloand ontogenetic) dimensions. Our hypothesis here aims to instantiate that the immune responses triggering is intimately linked to host’s spatial and temporal dimensions, which we will mainly refer to as the so-called host’s immunological biography [37]

Towards a liquid self

Findings

CONCLUSION AND PERSPECTIVE