Evidences for vagus nerve in maintenance of immune balance and transmission of immune information from gut to brain in STM-infected rats

Abstract

Aim: To determine whether Salmonella Typhimurium (STM)in gastrointestinal tract can induce the functional activation of brain, whether the vagus nerve involves in signaling immune information from gastrointestinal tract to brain and how it influences the immune function under natural infection condition.

Methods: Animal model of gastrointestinal tract infection in the rat was established by an intubation of Salmonella Typhimurium (STM) into stomach to mimic the condition of natural bacteria infection. Subdiagphragmatic vagotomy was performed in some of the animals 28 days before infection. The changes of Fos expression visualized with immunohistochemistry technique in hypothalamic paraventricular nucleus (PVN) and superaoptic nucleus (SON) were counted. Meanwhile, the percentage and the Mean Intensities of Fluorescent (MIFs) of CD4+ and CD8+ T cells in peripheral blood were measured by using flow cytometry (FCM), and the pathological changes in ileum and mesenteric lymph node were observed in HE stained sections.

Results: In bacteria-stimulated groups, inflammatory pathological changes were seen in ileum and mesenteric lymph node. The percentages of CD4+ T cells in peripheral blood were decreased from 42%+/-4.5% to 34%+/-4.9% (P<0.05) and MIFs of CD8+ T cells were also decreased from 2.9+/-0.39 to 2.1+/-0.36 (P<0.05) with STM stimulation. All of them proved that our STM-infection model was reliable. Fos immunoreactive (Fos-ir) cells in PVN and SON increased significantly with STM stimulation, from 189+/-41 to 467+/-62 (P<0.05) and from 64+/-21 to 282+/-47 (P<0.05) individually, which suggested that STM in gastrointestinal tract induced the functional activation of brain. Subdiagphragmatic vagotomy attenuated Fos expression in PVN and SON induced by STM, from 467+/-62 to 226+/-45 (P<0.05) and from 282+/-47 to 71+/-19 (P<0.05) individually, and restored the decreased percentages of CD4+ T cells induced by STM from 34%+/-4.9% to original level 44%+/-6.0% (P<0.05). In addition, subdiagphragmatic vagotomy itself also decreased the percentages of CD8+ T cells (from 28%+/-3.0% to 21%+/-5.9%, P<0.05) and MIFs of CD4+ (from 6.6+/-0.6 to 4.9+/-1.0, P<0.05) and CD8+ T cells (from 2.9+/-0.39 to 1.4+/-0.34, P<0.05). Both of them manifested the important role of vagus nerve in transmitting immune information from gut to brain and maintaining the immune balance of the organism.

Conclusion: Vagus nerve does involve in transmitting abdominal immune information into the brain in STM infection condition and play an important role in maintenance of the immune balance of the organism.

Figure 1

In Figures E1 and E3 show the normal structures of the villus and mesenteric lymph node in saline-injected rats; 2 and 4 show the villus and mesenteric lymph node in STM-challenged rats. 5 and 9 show Fos expression in PVN and SON respectively in NS + sham rats; 6 and 10 show Fos expressions in PVN and SON respectively in STM + sham rat; 7 and 11 show Fos expressions in PVN and SON respectively in STM + vagotomy rat; 8 and 12 show Fos expressions in PVN and SON respectively in NS + vagotomy rat. × 50

Figure 2

A: Percentages of blood CD4+ T cells. ^aP < 0.05 vs. STM + sham, ^bP < 0.05 vs NS + sham; B: The Mean Intensities of Fluorescence (MIFs) of blood CD4+ T cells. ^bP < 0.05 vs NS + sham; C: Percentages of blood CD8+ T cells. ^aP < 0.05 vs STM + sham, ^bP < 0.05 vs NS + sham; D: The Mean Intensities of Fluorescence (MIFs) of blood CD8+ T cells. ^aP < 0.05 vs STM + sham; ^bP < 0.05 vs NS + sham.