Requirements for innate immune pathways in environmentally induced autoimmunity

Abstract

There is substantial evidence that environmental triggers in combination with genetic and stochastic factors play an important role in spontaneous autoimmune disease. Although the specific environmental agents and how they promote autoimmunity remain largely unknown, in part because of diverse etiologies, environmentally induced autoimmune models can provide insights into potential mechanisms. Studies of idiopathic and environmentally induced systemic autoimmunity show that they are mediated by common adaptive immune response genes. By contrast, although the innate immune system is indispensable for autoimmunity, there are clear differences in the molecular and cellular innate components that mediate specific systemic autoimmune diseases, suggesting distinct autoimmune-promoting pathways. Some of these differences may be related to the bifurcation of toll-like receptor signaling that distinguishes interferon regulatory factor 7-mediated type I interferon production from nuclear factor-κB-driven proinflammatory cytokine expression. Accordingly, idiopathic and pristane-induced systemic autoimmunity require both type I interferon and proinflammatory cytokines whereas the less aggressive mercury-induced autoimmunity, although dependent on nucleic acid-binding toll-like receptors, does not require type I interferon but needs proinflammatory cytokines. Scavenger receptors and the inflammasome may contribute to silica-induced autoimmunity. Greater understanding of the innate mechanisms responsible for idiopathic and environmentally induced autoimmunity should yield new information into the processes that instigate and drive systemic autoimmunity.

The etiology of glomerulonephritis: roles of infection and autoimmunity

“…12 The first line of defense is the innate immune response, mediated by neutrophils, monocyte/macrophages, natural killer cells, complement, and cytokines, which is triggered by the binding of pathogen-associated molecular patterns to germline-encoded receptors known as pattern recognition receptors 13,14 that include Toll-like receptors (TLRs) and C-type lectin receptors capable of complement activation through the mannose-binding lectin pathway. 13 The innate immune system acts by identifying pathogen-associated molecular patterns, which include bacterial carbohydrates and peptides, mannose, and lipopolysaccharide.…”

Effects of Endocrine Disrupters on Immune Function and Inflammation

“…In contrast, type I interferon production does not appear to be involved [50]. The role of altered innate immune cell responses was also noted by Nyland et al [51], who found that prior mercury exposure caused a problematic, macrophage-driven response to viral infection in mice, leading to cardiac inflammation and an increased likelihood of autoimmunity.…”

“…Pollard and Kono [50] argue that mercury induces autoimmunity in individuals with a genetic predisposition and that the process involves alterations among innate immune cells that utilize nucleic acid-binding and toll-like receptors and need increased pro-inflammatory cytokine production. In contrast, type I interferon production does not appear to be involved [50].…”

Heavy metal intoxication compromises the host cytokine response inAscaris Suummodel infection

“…To this point it is not known how combination of contaminated environment and parasitism can infl uence development of immune response where regulatory (helper lymphocytes, cytokines) and effector (macrophages) components are important in the host defence against parasite. Specifi cally when these immune cells are also target structures for the heavy metals (Šoltys et al, 1997;Valko et al, 2005;Pollard & Kono, 2013). Mice are monogastric animals in which the liver and kidneys serve as detoxifi cation organs that help to eliminate toxic waste metabolites from the body.…”

“…Exposure of organisms to the heavy metal ions impairs hosts immunocompetence and increases susceptibility to the infections. Heavy metals also affect the cell physiology and modulate immune system responses (Valko et al, 2005;Holmes et al, 2009;Jomova & Valko, 2011;Hemdan et al, 2013;Pollard & Kono, 2013;Dvorožnáková & Jalčová, 2013). Due to high abundance of industrial heavy metals in exposed areas small mammals migrating in affected territories are suitable bioindicators of anthropogenic environmental pollution.…”