The Role of T Helper (TH)17 Cells as a Double-Edged Sword in the Interplay of Infection and Autoimmunity with a Focus on Xenobiotic-Induced Immunomodulation

Abstract

Extensive research in recent years suggests that exposure to xenobiotic stimuli plays a critical role in autoimmunity induction and severity and that the resulting response would be exacerbated in individuals with an infection-aroused immune system. In this context, heavy metals constitute a prominent category of xenobiotic substances, known to alter divergent immune cell responses in accidentally and occupationally exposed individuals, thereby increasing the susceptibility to autoimmunity and cancer, especially when accompanied by inflammation-triggered persistent sensitization. This perception is learned from experimental models of infection and epidemiologic studies and clearly underscores the interplay of exposure to such immunomodulatory elements with pre- or postexposure infectious events. Further, the TH17 cell subset, known to be associated with a growing list of autoimmune manifestations, may be the “superstar” at the interface of xenobiotic exposure and autoimmunity. In this review, the most recently established links to this nomination are short-listed to create a framework to better understand new insights into TH17's contributions to autoimmunity.

Heavy metal intoxication compromises the host cytokine response inAscaris Suummodel infection

“…Also it can alter the host-pathogen interactions or increase the susceptibility to diseases (Gardner et al, 2010). Hemdan et al (2007) in vitro demonstrated differences in Hg effect on the Th1/Th2 balance after different cells stimulation. Authors stated that a low dose of Hg turns up the immune response towards Th2 type in the case of absence of infl ammatory component, but not in the case of Th1 immune response induced by bacterial antigen.…”

“…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.…”

Nanoemulsion-based mucosal adjuvant induces apoptosis in human epithelial cells

“…In a previous study we documented that W 80 5EC NE is a potent adjuvant, inducing strong Th1 and Th17 immune responses [17]. The Th17 response, while constituting a protective arm defending the body against various infections, also functions as a double-edged sword constituting a risk factor that mediates the induction of autoimmune diseases [39]. Therefore, it is important to exclude the possibility that cell death caused by W 80 5EC NE may be involved in development of Th17 response associated with autoimmune or chronic inflammatory diseases.…”

Immunomodulatory Effects of Tigecycline in Balb/C Mice

“…Interleukin-2 and IL-17 have a pronounced role in the non-specific immune response and T cell differentiation. IL-2 is a regulatory cytokine produced by Th-1 cells that activates macrophages against intracellular antigens (26), since it mediates acute inflammation and DTH (27). IL-17 is a proinflammatory cytokine produced by Th-17, neutrophils and mast cells and is required for Th-17 development (28).…”