Thomas Pradeu

The speed of change: towards a discontinuity theory of immunity?

Immunology — though deeply experimental in everyday practice — is also a theoretical discipline. Recent advances in the understanding of innate immunity, how it is triggered and how it shares features that have previously been uniquely ascribed to the adaptive immune system, can contribute to the refinement of the theoretical framework of immunology. In particular, natural killer cells and macrophages are activated by transient modifications, but adapt to long-lasting modifications that occur in the surrounding tissue environment. This process facilitates the maintenance of self-tolerance while permitting efficient immune responses. In this Essay we extend this idea to other components of the immune system and we propose some general principles that lay the foundations for a unifying theory of immunity — the discontinuity theory. According to this theoretical framework, effector immune responses (namely, activated responses that lead to the potential elimination of the target antigen) are induced by an antigenic discontinuity; that is, by the sudden modification of molecular motifs with which immune cells interact.

Mutualistic viruses and the heteronomy of life.

Abstract Though viruses have generally been characterized by their pathogenic and more generally harmful effects, many examples of mutualistic viruses exist. Here I explain how the idea of mutualistic viruses has been defended in recent virology, and I explore four important conceptual and practical consequences of this idea. I ask to what extent this research modifies the way scientists might search for new viruses, our notion of how the host immune system interacts with microbes, the development of new therapeutic approaches, and, finally, the role played by the criterion of autonomy in our understanding of living things. Overall, I suggest that the recognition of mutualistic viruses plays a major role in a wider ongoing revision of our conception of viruses.

Immune-Mediated Repair: A Matter of Plasticity

Though the immune system is generally defined as a system of defense, it is increasingly recognized that the immune system also plays a crucial role in tissue repair and its potential dysregulations. In this review, we explore how distinct immune cell types are involved in tissue repair and how they interact in a process that is tightly regulated both spatially and temporally. We insist on the concept of immune cell plasticity which, in recent years, has proved fundamental for the success/understanding of the repair process. Overall, the perspective presented here suggests that the immune system plays a central role in the physiological robustness of the organism, and that cell plasticity contributes to the realization of this robustness.

The discontinuity theory of immunity

Similar to many other biological systems, the immune system can be seen as a change-detection system. Similar to many other biological systems, the immune system can be seen as a change-detection system. According to the discontinuity theory of immunity, the immune system responds to sudden changes in antigenic stimulation and is rendered tolerant by slow or continuous stimulation. This basic principle, which is supported by recent data on immune checkpoints in viral infections, cancers, and allergies, can be seen as a unifying framework for diverse immune responses.

Protective Microbiota: From Localized to Long-Reaching Co-Immunity

Resident microbiota do not just shape host immunity, they can also contribute to host protection against pathogens and infectious diseases. Previous reviews of the protective roles of the microbiota have focused exclusively on colonization resistance localized within a microenvironment. This review shows that the protection against pathogens also involves the mitigation of pathogenic impact without eliminating the pathogens (i.e., “disease tolerance”) and the containment of microorganisms to prevent pathogenic spread. Protective microorganisms can have an impact beyond their niche, interfering with the entry, establishment, growth, and spread of pathogenic microorganisms. More fundamentally, we propose a series of conceptual clarifications in support of the idea of a “co-immunity,” where an organism is protected by both its own immune system and components of its microbiota.

Immunological memory: What's in a name?

Immunological memory is one of the core topics of contemporary immunology. Yet there are many discussions about what this concept precisely means, which components of the immune system display it, and in which phyla it exists. Recent years have seen the multiplication of claims that immunological memory can be found in “innate” immune cells and in many phyla beyond vertebrates (including invertebrates, plants, but also bacteria and archaea), as well as the multiplication of concepts to account for these phenomena, such as “innate immune memory” or “trained immunity”. The aim of this critical review is to analyze these recent claims and concepts, and to distinguish ideas that have often been misleadingly associated, such as memory, adaptive immunity, and specificity. We argue that immunological memory is a gradual and multidimensional phenomenon, irreducible to any simple dichotomy, and we show why adopting this new view matters from an experimental and therapeutic point of view.

Understanding viruses: Philosophical investigations.

Viruses have been virtually absent from philosophy of biology. In this editorial introduction, we explain why we think viruses are philosophically important. We focus on six issues (the definition of viruses, the individuality and diachronic identity of a virus, the possibility to classify viruses into species, the question of whether viruses are living, the question of whether viruses are organisms, and finally the biological roles of viruses in ecology and evolution), and we show how they relate to classic questions of philosophy of biology and even general philosophy.

Re-thinking our understanding of immunity: Robustness in the tissue reconstruction system

Robustness, understood as the maintenance of specific functionalities of a given system against internal and external perturbations, is pervasive in todays biology. Yet precise applications of this notion to the immune system have been scarce. Here we show that the concept of robustness sheds light on tissue repair, and particularly on the crucial role the immune system plays in this process. We describe the specific mechanisms, including plasticity and redundancy, by which robustness is achieved in the tissue reconstruction system (TRS). In turn, tissue repair offers a very important test case for assessing the usefulness of the concept of robustness, and identifying different varieties of robustness.

Dissecting the Meanings of “Physiology” to Assess the Vitality of the Discipline

The vitality of physiology is currently under debate. Some say that physiology is a dying discipline in the era of molecular medicine and systems biology, whereas others claim that physiology remains a key biological and medical discipline, due in part to its integrative nature. In this conceptual review, we argue that any assessment of the vitality of physiology depends heavily on the definition of this discipline adopted. We examine two main conceptions of physiology, one focusing on its object (what physiology is about), and the other on the methods used (how physiologists study the biological reality). We contend that physiology no longer encompasses all biological disciplines and may no longer be the only synoptic biological science. However, far from indicating a sterility of this discipline, this situation should drive physiology to re-invent its relationship with these other biological domains.

The Multiple Layers of the Tumor Environment

The notion of tumor microenvironment (TME) has been brought to the forefront of recent scientific literature on cancer. However, there is no consensus on how to define and spatially delineate the TME. We propose that the time is ripe to go beyond an all-encompassing list of the components of the TME, and to construct a multilayered view of cancer. We distinguish six layers of environmental interactions with the tumor and show that they are associated with distinct mechanisms, and ultimately with distinct therapeutic approaches.