Infectome: a platform to trace infectious triggers of autoimmunity

Abstract

The "exposome" is a term recently used to describe all environmental factors, both exogenous and endogenous, which we are exposed to in a lifetime. It represents an important tool in the study of autoimmunity, complementing classical immunological research tools and cutting-edge genome wide association studies (GWAS). Recently, environmental wide association studies (EWAS) investigated the effect of environment in the development of diseases. Environmental triggers are largely subdivided into infectious and non-infectious agents. In this review, we introduce the concept of the "infectome", which is the part of the exposome referring to the collection of an individual's exposures to infectious agents. The infectome directly relates to geoepidemiological, serological and molecular evidence of the co-occurrence of several infectious agents associated with autoimmune diseases that may provide hints for the triggering factors responsible for the pathogenesis of autoimmunity. We discuss the implications that the investigation of the infectome may have for the understanding of microbial/host interactions in autoimmune diseases with long, pre-clinical phases. It may also contribute to the concept of the human body as a superorganism where the microbiome is part of the whole organism, as can be seen with mitochondria which existed as microbes prior to becoming organelles in eukaryotic cells of multicellular organisms over time. A similar argument can now be made in regard to normal intestinal flora, living in symbiosis within the host. We also provide practical examples as to how we can characterise and measure the totality of a disease-specific infectome, based on the experimental approaches employed from the "immunome" and "microbiome" projects.

Fig. 1

From exposome to infectome via microbiome. “Exposome” describes all environmental factors which we are exposed to in a lifetime, both exogenous and endogenous, infectious and non-infectious. Environmental exposures are basically subdivided into infectious and non-infectious agents. The concept of “infectome” that we introduce, describes the part of the exposome which refers to the collection of an individual's exposures to infectious agents participating in the pathogenesis of autoimmune disease. The infectome can be considered a part of “microbiome”, the collection of the microbial products which the human body is exposed to at a given time.

Fig. 2

Tracing infectious triggers of autoimmunity: the infectome from A to Z. Infectious agents participating in a series of events critical for the initiation of autoimmunity and the development of autoimmune disease can be traced at various time points. The traces of these infectious agents may help us to understand the extent of their involvement in the loss of immunological breakdown and/or the maintenance of autoreactive immune responses leading to self destruction. Infections, at times different of those responsible for the chain reaction of events that led to autoimmune disease, may participate in the remission/relapse clinical patterns seen after the onset of the disease.