The Impact of Microbiota-Immunity-Hormone Interactions on Autoimmune Diseases and Infection

Abstract

Autoimmune diseases are complex multifactorial disorders, and a mixture of genetic and environmental factors play a role in their onset. In recent years, the microbiota has gained attention as it helps to maintain host health and immune homeostasis and is a relevant player in the interaction between our body and the outside world. Alterations (dysbiosis) in its composition or function have been linked to different pathologies, including autoimmune diseases. Among the different microbiota functions, there is the activation/modulation of immune cells that can protect against infections. However, if dysbiosis occurs, it can compromise the host's ability to protect against pathogens, contributing to the development and progression of autoimmune diseases. In some cases, infections can trigger autoimmune diseases by several mechanisms, including the alteration of gut permeability and the activation of innate immune cells to produce pro-inflammatory cytokines that recruit autoreactive T and B cells. In this complex scenario, we cannot neglect critical hormones' roles in regulating immune responses. Different hormones, especially estrogens, have been shown to influence the development and progression of autoimmune diseases by modulating the activity and function of the immune system in different ways. In this review, we summarized the main mechanisms of connection between infections, microbiota, immunity, and hormones in autoimmune diseases' onset and progression given the influence of some infections and hormone levels on their pathogenesis. In detail, we focused on rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus.

Keywords: autoimmune diseases; hormones; immune system; infections; microbiota.

Figure 1

Infections can trigger or exacerbate autoimmune diseases through several mechanisms, leading to autoimmunity induction. (A) Molecular mimicry is the mechanism by which infectious antigens similar to self-molecules and presented by APCs can trigger T autoreactive cells, leading to the development of autoimmune diseases. (B) Bystander activation refers to the way in which over-reactive antiviral immune responses lead to the release of self-antigens and inflammatory cytokines from damaged tissue. Autoreactive T cells are then activated by APCs. (C) The epitope spreading model predicts that a persistent infection induces tissue damage and release of new self-antigens that are presented by APCs. Nonspecific triggering of several autoreactive T cells can lead to autoimmunity. APC = antigen-presenting cell.

Figure 2

Schematization of estrogen (E2) actions on B (green) and T (red) cells. There are several actions of estrogens on B cells such as the increase in cell number progenitors in the bone marrow, the enhanced survival in the spleen, and the induction of antibody production. Regarding E2’s effects on T cells, the promotion of cell activation, proliferation, survival, and differentiation have been described in Th-1 subtype. Extrathymic cell differentiation in the liver was observed. All these features could lead to the predisposition to autoimmunity and disease development when an imbalance occurs.