de Meis Juliana, Ferreira Lidia M S, Guillermo Landi V C, Silva Elisabeth M, Dosreis George A, Lopes Marcela F
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
Eur J Immunol. 2008 Jan;38(1):139-46. doi: 10.1002/eji.200737582.
Infection with Trypanosoma cruzi causes expansion of subcutaneous (SLN) and atrophy of mesenteric (MLN) lymph nodes. Here we show that excision of MLN increased parasitemia in T. cruzi-infected mice. We then studied how apoptosis of MLN cells affects immune responses to infection. T cell apoptosis increased in the MLN compared to SLN in T. cruzi-infected mice. Absolute numbers of naïve T cells decreased, and activated T cells failed to accumulate in MLN during infection. In addition, activated T cells from MLN produced less IL-2, IFN-gamma, IL-4, and IL-10 than T cells from SLN. Treatment with IL-4 or with caspase-9 inhibitor increased the recovery of viable T cells in vitro. Treatment with caspase-9 inhibitor also increased the production of cytokines by MLN T cells from infected mice. Moreover, injection of a pan caspase inhibitor prevented MLN atrophy during T. cruzi infection. Caspase-9, but not caspase-8, inhibitor also reduced MLN atrophy and increased the recovery of naïve and activated T cells from MLN. These findings indicate that caspase-mediated apoptosis and defective cytokine production are implicated in MLN atrophy and affect immune responses to T. cruzi infection.
克氏锥虫感染会导致皮下淋巴结（SLN）肿大和肠系膜淋巴结（MLN）萎缩。在此我们表明，切除MLN会增加克氏锥虫感染小鼠的寄生虫血症。然后我们研究了MLN细胞的凋亡如何影响对感染的免疫反应。在克氏锥虫感染的小鼠中，与SLN相比，MLN中的T细胞凋亡增加。幼稚T细胞的绝对数量减少，并且在感染期间活化的T细胞未能在MLN中积累。此外，来自MLN的活化T细胞产生的IL-2、IFN-γ、IL-4和IL-10比来自SLN的T细胞少。用IL-4或半胱天冬酶-9抑制剂处理可增加体外存活T细胞的恢复。用半胱天冬酶-9抑制剂处理还可增加感染小鼠的MLN T细胞产生的细胞因子。此外，注射泛半胱天冬酶抑制剂可预防克氏锥虫感染期间的MLN萎缩。半胱天冬酶-9抑制剂而非半胱天冬酶-8抑制剂也可减轻MLN萎缩，并增加MLN中幼稚和活化T细胞的恢复。这些发现表明，半胱天冬酶介导的凋亡和细胞因子产生缺陷与MLN萎缩有关，并影响对克氏锥虫感染的免疫反应。
