Interferon‐γ and Interleukin‐12 Genes are Preferentially Expressed During Early Experimental African Trypanosomiasis and Suppressed by Denervation of the Spleen

Abstract

The cross talk between the central nervous system (CNS) and the immune system includes among others, the modulation of immune responses by the autonomic nervous system. Here, we investigated the effects of a splenic denervation on cytokine induction in early experimental African trypanosomiasis. Profiles of the cytokine mRNA expression for interleukin (IL)‐4, interleukin (IL)‐6, interleukin (IL)‐10, interleukin (IL)‐12, tumour necrosis factor (TNF)‐α, tumour necrosis factor (TNF)‐β, transforming growth factor (TGF)‐β and interferon (IFN)‐γ were examined at 4 h, 8 h and 12 h postinfection (p.i.), and in noninfected controls. Only IFN‐γ and IL‐12 were significantly expressed over noninfected controls. Already at 4 h p.i. both cytokines were expressed and showed more increased levels at 12 h. Sympathetic denervation of the spleen markedly reduced the mRNA expression for both IFN‐γ and IL‐12. Con A was used as a positive control and showed an enhanced mRNA expression, which was also suppressed by a splenic denervation. To demonstrate that the mRNA expression had resulted in a cytokine production, we looked for the protein level of IFN‐γ at 4 h p.i. by immunohistochemistry and found increased levels of IFN‐γ, which was also inhibited by the denervation. Sham‐operated animals exhibited similar responses as the nondenervated controls. Our data present for the first time very early kinetics for a cytokine gene expression during an experimental African trypanosomiasis. Furthermore, the data suggest a regulatory role for the autonomic nervous system on cytokine responses at both the mRNA and the protein levels.

Interferon-Gamma Release in Sympathetically Denervated Rat Submaxillary Lymph Nodes

“…For example, several days after the surgical denervation of the rat spleen, a suppression of the effect of Con A on splenic IFN-Á gene expression was observed [16]. This indicates, in agreement with the present study, the existence of a long-term depressive effect of sympathetic denervation on IFN-Á release.…”

Protective Effect of Humus Extract Against Trypanosoma brucei Infection in Mice

“…3). IL-12 is involved in the initiation of immune response and the switching of the Th2 response to Th1 type [10], since IL-12 is a strong stimulator of IFN-γ production during infections. On the other hand, IL-12-independent IFN-γ can be produced, also resulting in resistance against T. brucei [1] and Trypanosoma cruzi infection [11].…”

DNA from Protozoan ParasitesBabesia bovis, Trypanosoma cruzi, andT. bruceiIs Mitogenic for B Lymphocytes and Stimulates Macrophage Expression of Interleukin-12, Tumor Necrosis Factor Alpha, and Nitric Oxide

“…3). Activation of macrophage cytokines by protozoan parasites including B. bovis, T. brucei, and T. cruzi is well documented (13,25,30,37). Among the parasite-derived molecules known to activate macrophages are membrane-derived glycolipids such as glycosylphosphatidylinositol (GPI) moieties (13,45).…”

“…IL-12, induced by B. bovis, T. brucei and T. cruzi parasites (13,30,37), is a key type 1 cytokine that stimulates IFN-␥ production by NK cells and T cells and results in macrophage activation and production of molecules, such as NO, that are directly microbicidal (47). Several reports indicated that type 1 immune responses involving IL-12, TNF-␣, and NO are protective in experimental babesiosis and trypanosomiasis.…”