Mercury exposure as a model for deviation of cytokine responses in experimental Lyme arthritis: HgCl2 treatment decreases T helper cell type 1-like responses and arthritis severity but delays eradication of Borrelia burgdorferi in C3H/HeN mice

Abstract

SummaryLyme borreliosis is a complex infection, where some individuals develop so-called 'chronic borreliosis'. The pathogenetic mechanisms are unknown, but the type of immune response is probably important for healing. A strong T helper cell type 1 (Th1)-like response has been suggested as crucial for eradication of Borrelia and for avoiding development of chronic disease. Many studies aimed at altering the Th1/Th2 balance in Lyme arthritis employed mice deficient in cytokine genes, but the outcome has not been clear-cut, due possibly to the high redundancy of cytokines. This study aimed at studying the importance of the Th1/Th2 balance in murine Borrelia arthritis by using the Th2-deviating effect of subtoxic doses of inorganic mercury. Ninety-eight C3H/HeN mice were divided into four groups: Borrelia-infected (Bb), Borrelia-infected exposed to HgCl2 (BbHg), controls exposed to HgCl2 alone and normal controls. Mice were killed on days 3, 16, 44 and 65 post-Borrelia inoculation. Arthritis severity was evaluated by histology, spirochaetal load determined by Borrelia culture, IgG2a-and IgE-levels analysed by enzymelinked immunosorbemt assay (ELISA) and cytokine-secreting cells detected by enzyme-linked immunospot (ELISPOT). BbHg mice showed less severe histological arthritis, but delayed eradication of spirochaetes compared to Bb mice, associated with increased levels of IgE (Th2-induced) and decreased levels of IgG2a (Th1-induced), consistent with a Th2-deviation. Both the numbers of Th1 and Th2 cytokine-secreting cells were reduced in BbHg mice, possibly explained by the fact that numbers of cytokine-secreting cells do not correlate with cytokine concentration. In conclusion, this study supports the hypothesis that a Th1-like response is required for optimal eradication of Borrelia.

Lyme Disease: A Review

“…The adaptive immune response, particularly humoral response, is important in controlling the severity of Lyme disease in mice, but the bacteria can survive despite eliciting a strong antibody response, possibly because of immune evasion by modulating gene expression. In mice, a stronger initial T-helper type 1 (Th1) response seems to be important for controlling the infection [18,19]. Interestingly, Ixodes tick saliva has been shown to induce a Th2 response that facilitates infection [18,20].…”

Neuroimmunology

“…When rats were exposed to aluminum, the level of NE correlated negatively with proportions of CD4 + T lymphocytes, as well as T and B lymphocyte proliferation (Hu et al, 2013), suggesting that an aluminum-induced increase in NE may have an effect on inducing immunosuppression (Hu et al, 2013). However, the neurotoxic effects of these metals on neurotransmission are well characterized (Chang, 1977;Florea and Busselberg, 2006;Lynes et al, 2006) and, therefore, may contribute to some of the immune suppression observed after in vivo exposure to this metal (Dietert et al, 2004;Ekerfelt et al, 2007;Lawrence and Mccabe, 2002;Lee and Dietert, 2003;Lynes et al, 2006;Silbergeld et al, 2005).…”

Introduction, Sign, Symptoms, Prevention and Management of Lyme Disease Caused by <i>Borrelia burgdorferi</i> Channeled through <i>Ixodes</i> Ticks as Vector. A Review

“…If health-condition is better than before; it shows that all bacteria have been killed. If health is not getting normalize one should refer to some specialist [58].…”