Prologue: The Guardians of Homeostasis

Abstract

Homeostasis describes the phenomenon by which an organism sustains nearly constant conditions in the internal environment of the self by reacting and counteracting against any perturbation, stress, or injury arising from either inside, for example, caused by intrinsic metabolic irregularities, or fluxing in from the exterior world in the form of inciting insults including infectious, sterile/physical, or psychological injuries. On a broader sense, the concept of homeostasis goes back to Charles Darwin’s Theory of Evolution that was combined with the recognition that the body chemistries of many disparate species were remarkably similar. Darwin’s early notions about the existence of life on our planet probably stimulated Claude Bernard to postulate in 1854 the principal idea of “maintenance of life by the homeostasis of stable interior environment” (“milieu interieur”) that would allow biological functions to proceed despite variations in the external environment. Homeostasis operates at three levels by distinguishing between systemic, tissue, and cellular homeostasis. There are four major tightly linked homeostatic control systems which take care of surveillance of homeostasis and initiate stress responses in case of a perturbation of homeostasis: (1) the central nervous/psychoneural system, (2) the endocrine system, (3) the (innate) immune system, and (4) the microbiota. With the recent appreciation of the danger/injury model, the innate immune system is regarded as a highly sensitive organ of perception that recognized any cell stress and/or tissue injury, be it of infectious or sterile nature. The core of this homeostatic system refers to pattern recognition molecules (PRMs) which possess the ability to sense ancient molecular motifs derived from microbes (MAMPs) as well as sterile insult-induced damage-associated molecular patterns (DAMPs).