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.

Role of X-Chromosome encoded miRNAs in Autoimmunity: Suppressing the suppressor and Female Predisposition

“…However, it is becoming increasingly clear that synergistic interactions between adaptive and innate immune functions induce autoimmunity [1,2]. Association of the infectious agents with disease manifestation has been described for majority of the AID studied [1][2][3]. Anti infective mechanisms of the innate immune system; cytolytic processes and generation of harmful agents such as proteases and reactive oxygen species can damage host cells and tissues.…”

“…A study using Tlr7 transgenic [tg] mouse model by Walsh et al, has recently demonstrated that the development of Tlr7 induced B cell mediated lupus-like autoimmunity requires B cell interactions with T cells as well as innate immune cells [12]. TLR signaling cascade is negatively regulated at several levels by [1] proteasome-degradation of signal molecules mediated by E3 ubiquitin ligases such as SOCS and CBLB, [2] dephosphorylation of proteins in the cascade by the action of phosphatases, [3] transcription regulation and, [4] miRNA mediated downregulation of signal proteins. miR-155, miR-146a, miR-21 are some of the miRNAs involved in regulation of TLR signaling [13].…”

Bacterial Translocation from Intestine: Microbiological, Immunological and Pathophysiological Aspects

“…Нахождение граней между физиологическими и патологическими воспалительными реакциями в ткане-вых структурах, контактирующих с естественным микро-биотическим окружением, несомненно, будет предме-том дальнейших исследований в экспериментальной и теоретической патологии. Очевидно, что общепринятое понятие нормы требует углубленного методологического анализа с учетом постоянного динамического взаимодей-ствия организма хозяина с пусковыми факторами среды, важнейшим компонентом которых являются микробио-тические: их также можно рассматривать в качестве экс-посом (сумма факторов среды как экзогенных, так и эндогенных), с воздействием которых организм хозяина сталкивается на протяжении жизненного цикла [26]. В этом отношении гнотобиотические модели обеспечивают уникальный биологический инструмент и дополнитель-ный контроль в изучении сложной цепи взаимодействия про-и эукариотических организмов.…”

The spectrum between antiphospholipid syndrome and systemic lupus erythematosus

“…Numerous infectious agents have been related to autoimmunity and production of autoantibodies [20][21][22] as well as with evident diseases such as SLE and APS [23][24][25][26][27]. Additional factors such as hormones [28,29], vitamins such as vitamin D [30][31][32], sun exposure, etc.…”