From rejection to symbiosis. Human-infectious agents relations : a general theory of physiology and pathology. The contribution of tropical medicine.

Abstract

In this paper, the word symbiosis (from the Greek Sumbiōsis) is used in its original sense and refers to all organisms which interact with each other, whether this association is beneficial, neutral or harmful to the host (mutualism, commensalism and parasitism). Symbiosis is found in every aspect of the living world. It is seen between infectious agents, in tropical disease vectors, in the human body and in illnesses. Immune-dependent symbiosis between infectious agents and the host is an opposite and complementary mechanism to defense and rejection immunity. This duality is found in many biological functions. Our comprehensive, compelling theory provides an overview of the different sites and mechanisms where symbiosis may occur. These symbioses are ongoing, fourdimensional evolutionary processes. They are gradually shifting away from phenotypic symbioses, including exosymbioses (metazoans, protozoa, yeasts, bacteria, viruses), tissular endosymbioses (metazoans, yeast), toward cytoplasmic and nuclear endosymbioses (protozoa, yeasts, bacteria, RNA viruses), before finally arriving at genomic endosymbioses (mitochondrial DNA, DNA viruses, retroviruses, transposable elements), which is the ultimate goal of symbiotic evolution, giving rise to new human genes. The phenotype/genotype boundary is thus traversable. A immunological process that initially takes an immunopathologic inflammatory form, but develops into a non-inflammatory immuno-physiological state. A process that leads from parasitism to mutualism and commensalism, and ultimately to the emergence of new species. This article hinges on the primary author’s extensive experience in tropical medicine allied with meticulous bibliographic research. Our intention is to offer a fresh perspective on the different forms of physiological and pathological symbioses in humans and illustrate them with examples. The general control mechanisms of symbiosis are discussed including immune tolerance and rejection. Innate immunity requires an assumption about the evolutionary mechanisms involved in recognition of immune innate material. In adaptive immunity we develop the hypothetical role of antibody dependent cell tolerance (ADCT) in which cytophilic antibodies support immune-dependent symbiosis. This includes then the crucial role of growth and differentiation factors in symbiotic mechanisms. We will list ten areas of research and application in fundamental science (self-genomics, immune innate material), epidemiology, prevention (nuclear endomembrane, symbiogenic vaccination) and treatment (including differentiation therapy), which bring together internists, infectious disease specialists, oncologists, biologists, immunologists, geneticists, epidemiologists, nutritionists, botanists and evolutionary scientists.