Hypothalamus-pituitary-adrenal axis during Trypanosoma cruzi acute infection in mice
Hypothalamus-pituitary-adrenal axis during Trypanosoma cruzi acute infection in mice
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DOI：
10.1016/j.jneuroim.2005.08.015
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发表时间：
2006-04-01
影响因子：
3.3
通讯作者：
Savino, W
中科院分区：
文献类型：
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作者：
Corrêa-De-Santana, E;Paez-Pereda, M;Savino, W
神经内分泌和免疫系统之间的功能相互作用是由相似的配体和受体介导的，它们建立了与动态平衡相关的双向通信。在此，我们研究了小鼠急性感染克氏锥虫后下丘脑-垂体-肾上腺(HPA)轴的变化。在感染小鼠的肾上腺中可见寄生虫，而在感染小鼠的肾上腺和脑下垂体中均可检测到T ruzi特异的PCR基因扩增产物。感染动物的脑垂体和肾上腺的组织学和免疫组织化学分析显示，血管淤滞，细胞外基质蛋白纤维连接蛋白和层粘连蛋白上调，以及T细胞和巨噬细胞的浸润。在功能上，我们分别检测到下丘脑和血清中CRH的减少和皮质酮含量的增加。相反，我们没有发现感染动物血清中ACTH的量有明显的变化，而血清中糖皮质激素刺激细胞因子IL-6(白介素6)的水平与对照组相比有所增加。当我们分析T CRUZI对产生ACTH的AtT-20细胞株的影响时，感染的培养物与对照组相比，ACTH和前阿片黑素皮质素的产生水平较低。在这些细胞中，我们观察到STAT-3的强烈磷酸化，以及细胞因子信号转导抑制因子3(SOCS-3)和激活的STAT-3抑制因子(PIAS-3)IL-6的合成增加，这可以解释ACTH产生的部分阻断。综上所述，我们的数据显示，在急性克氏支原体感染期间，HPA轴发生了变化。提示寄生虫对内分泌动态平衡的直接和间接影响。(C)2005 Elsevier B.V.保留所有权利。
Functional interactions between neuroendocrine and immune systems are mediated by similar ligands and receptors, which establish a bidirectional communication that is relevant for homeostasis. We investigated herein the hypothalamus-pituitary-adrenal (HPA) axis in mice acutely infected by Trypanosoma cruzi, the causative agent of Chagas' disease. Parasites were seen in the adrenal gland, whereas T cruzi specific PCR gene amplification product was found in both adrenal and pituitary glands of infected mice. Histological and immunohistochemical analyses of pituitary and adrenal glands of infected animals revealed several alterations including vascular stasis, upregulation of the extracellular matrix proteins fibronectin and laminin, as well as T cell and macrophage infiltration. Functionally, we detected a decrease in CRH and an increase in corticosterone contents, in hypothalamus and serum respectively. In contrast, we did not find significant changes in the amounts of ACTH in sera of infected animals, whereas the serum levels of the glucocorticoid-stimulating cytokine, IL-6 (interleukin-6), were increased as compared to controls. When we analyzed the effects of T cruzi in ACTH-producing AtT-20 cell line, infected cultures presented lower levels of ACTH and pro-opiomelanocortin production when compared to controls. In these cells we observed a strong phosphorylation of STAT-3, together with an increased synthesis of IL-6, suppressor of cytokine signaling 3 (SOCS-3) and inhibitor of activated STAT-3 (PIAS-3), which could explain the partial blockage of ACTH production. In conclusion, our data reveal that the HPA axis is altered during acute T cruzi infection.. suggesting direct and indirect influences of the parasite in the endocrine homeostasis. (c) 2005 Elsevier B.V. All rights reserved.