Effect of 6-Hydroxydopamine on Host Resistance againstListeria monocytogenesInfection

Abstract

Recent studies have shown that immunocompetent cells bear receptors of neuropeptides and neurotransmitters and that these ligands play roles in the immune response. In this study, the role of the sympathetic nervous system in host resistance against Listeria monocytogenes infection was investigated in mice pretreated with 6-hydroxydopamine (6-OHDA), which destroys sympathetic nerve termini. The norepinephrine contents of the plasma and spleens were significantly lower in 6-OHDA-treated mice than in vehicle-treated mice. The 50% lethal dose of L. monocytogenes was about 20 times higher for 6-OHDA-treated mice than for vehicletreated mice. Chemical sympathectomy by 6-OHDA upregulated interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-␣) production in enriched dendritic cell cultures and gamma interferon (IFN-␥) and TNF-␣ production in spleen cell cultures, whereas chemical sympathectomy had no apparent effect on phagocytic activities, listericidal activities, and nitric oxide production in peritoneal exudate cells and splenic macrophages. Augmentation of host resistance against L. monocytogenes infection by 6-OHDA was abrogated in IFN-␥ ؊/؊ or TNF-␣ ؊/؊ mice, suggesting that upregulation of IFN-␥, IL-12, and TNF-␣ production may be involved in 6-OHDA-mediated augmentation of antilisterial resistance. Furthermore, adoptive transfer of spleen cells immune to L. monocytogenes from 6-OHDA-treated mice resulted in untreated naive recipients that had a high level of resistance against L. monocytogenes infection. These results suggest that the sympathetic nervous system may modulate host resistance against L. monocytogenes infection through regulation of production of IFN-␥, IL-12, and TNF-␣, which are critical in antilisterial resistance.

Sympathetic modulation of immunity: Relevance to disease

“…Ablation of the SNS prior to gram-negative bacteria challenge, such as Listeria monocytogenes, Pseudomonas aeruginosa or Escherichia coli, reduces bacterial dissemination [299][300][301][302]. This SNS effect is mediated via increased secretion of peritoneal TNF, phagocytic activity, and influx of monocytes into the peritoneal cavity [302].…”

β2-Adrenoreceptor Agonist Inhibits Antigen Cross-Presentation by Dendritic Cells

“…In particular, catecholamines induce elevation in the number of circulating lymphocytes both in humans (4) and mice (5). The global effect of b-agonists on immunity was mainly studied by chemically depleting natural catecholamine stocks using 6-hydroxydopamine, which results in increased innate immune responses against bacteria (6), increased adaptive immune responses against virus (7), and decreased immune responses against Gram-positive bacteria (7)(8)(9). Additionally, surgical removal of the ocular sympathetic nerve affects the generation and maintenance of immune privilege in the eye (10).…”

Amebic Liver Abscess in Rat: Morphological Evidence of Innate Immune Modulation by the Sympathetic Nervous System

“…On the other hand, in rat models that are resistant to amoebiasis it is known that immune response eliminate the most of the amebic load at the first 24 h, with high recruitment of neutrophils in acute phase, and lately with increment of macrophages (Pérez-Tamayo et al;Tsutsumi et al, 1990). Miura et al (2001) demonstrated that chemical sympathectomy with 6-OHDA improves survival in mice infected with Listeria monocytogenes, with augmented production of IFN-g, IL-1b, IL-2, IL-4 and IL-6; conversely, noradrenaline inhibited their secretion, but no change was observed in IL-4. Moreover, sympathetic denervation impacted T cells activity by reduction of reactivity in mice before sensitization with trinitrophenil hapten (Madden et al, 1989).…”