Protein malnutrition promotes dysregulation of molecules involved in T cell migration in the thymus of mice infected with Leishmania infantum.
Protein malnutrition promotes dysregulation of molecules involved in T cell migration in the thymus of mice infected with Leishmania infantum.
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DOI：
10.1038/srep45991
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发表时间：
2017-04-11
影响因子：
4.6
通讯作者：
Cuervo P
中科院分区：
文献类型：
--
作者：
Losada-Barragán M;Umaña-Pérez A;Cuervo-Escobar S;Berbert LR;Porrozzi R;Morgado FN;Mendes-da-Cruz DA;Savino W;Sánchez-Gómez M;Cuervo P
蛋白质营养不良是发展中国家营养不良的最有害原因，被认为是临床内脏利什曼病(VL)发展的主要危险因素。蛋白质营养不良和感染婴儿利什曼原虫导致淋巴组织紊乱，包括胸腺和脾细胞和淋巴细胞亚群的变化。在这里，我们报告了蛋白质营养不良通过降低感染动物的CCL5、CXCL12、IGF1、CXCL9和CXCL10蛋白水平来改变胸腺趋化因子。然而，T细胞保持其迁移能力，因为它们能够在体外迁移对趋化刺激的反应，这表明营养不良可能损害胸腺微环境，改变体内胸腺细胞的迁移。趋化因子蛋白水平的降低伴随着脾内寄生虫负荷的早期增加。这些结果表明，营养不良的前提条件是通过改变T细胞迁移和干扰缺乏蛋白质的动物控制寄生虫传播和增殖的能力来影响对幼虫的细胞免疫反应。我们的数据提供了涉及中央和外周T细胞的T淋巴细胞迁移障碍的证据，这可能有助于营养不良个体发生的VL的病理生理学。
Protein malnutrition, the most deleterious cause of malnutrition in developing countries, has been considered a primary risk factor for the development of clinical visceral leishmaniasis (VL). Protein malnutrition and infection with Leishmania infantum leads to lymphoid tissue disorganization, including changes in cellularity and lymphocyte subpopulations in the thymus and spleen. Here we report that protein malnutrition modifies thymic chemotactic factors by diminishing the CCL5, CXCL12, IGF1, CXCL9 and CXCL10 protein levels in infected animals. Nevertheless, T cells preserve their migratory capability, as they were able to migrate ex vivo in response to chemotactic stimuli, indicating that malnutrition may compromise the thymic microenvironment and alter in vivo thymocyte migration. Decrease in chemotactic factors protein levels was accompanied by an early increase in the parasite load of the spleen. These results suggest that the precondition of malnutrition is affecting the cell-mediated immune response to L. infantum by altering T cell migration and interfering with the capacity of protein-deprived animals to control parasite spreading and proliferation. Our data provide evidence for a disturbance of T lymphocyte migration involving both central and peripheral T-cells, which likely contribute to the pathophysiology of VL that occurs in malnourished individuals.