Low-dose mercury heightens early innate response to coxsackievirus infection in female mice

Abstract

Objective Mercury is a ubiquitous environmental contaminant with toxic outcomes over a range of exposures. In this study, we investigated the effects of mercury exposure on early immune responses to coxsackievirus B3 (CVB3) infection in a murine model of autoimmune heart disease. Materials and Methods Female BALB/c mice, susceptible to CVB3-induced autoimmune myocarditis, were treated with mercuric chloride (200 μg/kg body weight every other day for 2 weeks) prior to infection with CVB3. Six hours post-infection, immune cells were isolated from the spleen and peritoneum for flow cytometry, gene expression, and cytokine profiling. Thirty-five days post-infection, hearts were collected for histological examination of immune cell infiltration. Results As for male mice, mercury exposure significantly increased autoimmune myocarditis and immune infiltration into the heart. During the innate response six hours post-infection, mercury increased expression of co-stimulatory molecules and innate immune receptors on peritoneal macrophages. At the same time point, the alternatively-activated macrophage gene, arginase, was increased while the classically-activated macrophage gene, inducible nitric oxide synthase, was unaffected. Expression of activation markers were decreased on peritoneal B cells with mercury exposure while T cells were unaffected. Mercury increased production of pro-inflammatory mediators in the spleen. Macrophage-recruiting chemokines and activating cytokines such as CCL2, CCL4, and IL-6 were increased with mercury following CVB3 infection. Conclusions Thus, mercury treatment exacerbates autoimmune myocarditis in female mice and alters early innate signaling on peritoneal macrophages. Mercury also modulates the cytokine profile in the spleen toward a macrophage-activating milieu, and upregulates alternatively-activated macrophage genes, providing evidence that mercury exposure promotes inflammation in the context of infection.

Toxic metal exposure as a possible risk factor for COVID-19 and other respiratory infectious diseases

“… Farsalinos et al, 2020 , Heo et al, 2017 , Li et al, 2017 , Li et al, 2020 , Penta et al, 2015 , Singhal, 2020 , Tinkov et al, 2018 , Tsatsakis et al, 2020 , Wu et al, 2020 , Xu et al, 2017 , Yang et al, 2019 Xu et al, 2017, Li et al, 2020, .…”

Costimulation blockade by combining CTLA4Ig with anti-CD40L mAb markedly inhibits the inflammatory response of experimental autoimmune myocarditis

“…Cytokines play an important role in the development and severity of autoimmune myocarditis. 9 Th1 cytokines, such as IFN-γ, have predominant functions during the progressive phase of acute myocarditis, [10][11][12] while Th2 cytokines such as IL-4 have an inhibitory effect in EAM. 3 In line with Massilamany et al, 13 this study showed that IFN-γ was decreased while IL-4 was increased after single intervention.…”