title: Apoptosis differentially regulates mesenteric and subcutaneous lymph node immune responses to Trypanosoma cruzi.
abstract: 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.
authors: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
authors: Juliana
authors: J
authors: de Meis
authors: Lidia M S
authors: LM
authors: Ferreira
authors: Landi V C
authors: LV
authors: Guillermo
authors: Elisabeth M
authors: EM
authors: Silva
authors: George A
authors: GA
authors: Dosreis
authors: Marcela F
authors: MF
authors: Lopes
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001284:Atrophy; D020169:Caspases / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014355:Chagas Disease / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D008198:Lymph Nodes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008643:Mesentery / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D014349:Trypanosoma cruzi
chemical_list: D016207:Cytokines; D004791:Enzyme Inhibitors; D020169:Caspases