Apoptosis differentially regulates mesenteric and subcutaneous lymph node immune responses to Trypanosoma cruzi

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 naive 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 naive 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.