ART and immunology

Abstract

Art enables us to find ourselves and lose ourselves at the same time. Thomas MertonInfectious diseases have played a major role in natural selection, shaping the evolution of numerous traits in multicellular organisms. In turn, diverse defense mechanisms have evolved to afford survival and reproduction in the face of pathogen challenges. These mechanisms can be categorized into three strategies: avoidance of pathogen exposure, resistance to infection once it has taken place, and tolerance to the pathogen's presence. Avoidance is an essential part of the behavioral repertoire required for survival. Avoidance mechanisms, such as evasive maneuvering, production of repellants, and promotion of good hygiene practices, are based on remote detection of pathogens, usually using various molecular proxies, such as metabolites that produce characteristic odors. Resistance mechanisms involve the destruction of the pathogen and limitation of its spread; these are the function of the immune system, and encompass the processes that are commonly referred to as immunity. Tolerance – distinct from the processes of immune tolerance – refers to a collection of mechanisms that foster the return or maintenance of homeostasis by promoting tissue protection and repair, and otherwise minimizing damage caused by pathogens or the immune responses they elicit. A recent Marion Koshland Symposium on ‘The ART of Pathogen Handling’ (where ART stands for Avoidance-Resistance-Tolerance) at The University of Chicago brought together investigators who work in these three areas, with the goal of providing a forum for discussion that would integrate concepts brought forth by these fields of research. This Symposium served also as inspiration for this Special Issue of Trends in Immunology, which aims to present an expanded view of immunology that incorporates strategies of host defense from an organismal, ecological, and evolutionary perspective.Avoidance is likely the most cost-effective way of dealing with pathogens and parasites. Articles in this issue examine some core questions in pathogen avoidance behavior: What are the neurological mechanisms underlying aversive learning, and are these connected to mechanisms of pathogen sensing that trigger immune responses (Meisel and Kim, this issue)?; How does aversive behavior, triggered by disgust and repulsion of what is perceived as diseased or contagious, impact broader behavioral patterns at the individual level and at the social level, and how do these behaviors relate to protection from infection and to the shape and size of societal structures (Curtis, this issue) (Cremer, this issue)? In tackling these questions, these authors bring to bear the distinct strengths and opportunities afforded by model organisms such as Caenorhabditis elegans and ants, and highlight what we can learn from human behavioral patterns and the epidemiology of different diseases.Resistance, involving both innate and adaptive immune mechanisms, has been the most studied component of ART. This issue spotlights the complexities inherent to this battle. Veldhoen and Heeney (this issue) highlight the challenge of understanding the impact of immunity during co-infection by discussing instances where the immune response to helminth infection triggers the reactivation of latent viral infections. Plants lack mobile inflammatory cells and their strategy for the recognition of pathogens is built around detection of their virulence activity and associated damage rather than direct recognition of pathogen associated molecular patterns by specialized immune cells; yet, metazoa and planta appear to have arrived at conceptually similar solutions to the problem of infection, as discussed by Kagan (this issue). Finally, based on studies in hydra and its commensals, Bosch (this issue) proposes that innate immunity arose not as an adversary to pathogenic microbes, but rather from the need to harness mutualistic symbionts. This perspective bears important implications, especially as we aim to understand our relationship with our microbiota.Whereas resistance and tolerance can be thought of as distinct strategies, and are often studied separately, many of the same cells and molecular pathways are involved. Soares (this issue) proposes that resistance and tolerance are not entirely distinct defense strategies, but are rather an interweaving set of mechanisms, many broadly conserved, aimed at damage control and return to homeostasis. This continuum suggests co-regulation of these responses, and insight into the mechanisms involved will represent an important step forward towards a broader understanding of immunity and physiology.We would like to thank the distinguished experts who contributed to this issue as authors and reviewers. We hope that you, the readers, may find in these articles inspiration for asking new questions and revisiting older questions in immunology, and that you bring to these an expanded perspective that integrates our growing understanding of the complex strategies of host defense. In tackling these questions we may find ourselves at the edges of immunology – an exciting place to be.