Angiotensin II Is a New Component Involved in Splenic T Lymphocyte Responses during Plasmodium berghei ANKA Infection

作者：Silva Filho Joao Luiz; Souza Mariana Conceicao; Ferreira DaSilva Claudio Teixeira; Silva Leandro Souza; Souza Costa Maria Fernanda; Padua Tatiana Almeida; Henriques Maria das Gracas; Morrot Alexandre; Savino Wilson; Caruso Neves Celso; Sa Pinheiro Ana Acacia

来源：PLos One, 2013, 8(4): e62999.

DOI：10.1371/journal.pone.0062999

The contribution of T cells in severe malaria pathogenesis has been described. Here, we provide evidence for the potential role of angiotensin II (Ang II) in modulating splenic T cell responses in a rodent model of cerebral malaria. T cell activation induced by infection, determined by 3 to 4-fold enhancement in CD69 expression, was reduced to control levels when mice were treated with 20 mg/kg losartan (IC50 = 0.966 mg/kg/d), an AT(1) receptor antagonist, or captopril (IC50 = 1.940 mg/kg/d), an inhibitor of angiotensin-converting enzyme (ACE). Moreover, the production of interferon-gamma and interleukin-17 by CD4(+) T cells diminished 67% and 70%, respectively, by both treatments. Losartan reduced perforin expression in CD8(+) T cells by 33% while captopril completely blocked it. The upregulation in chemokine receptor expression (CCR2 and CCR5) observed during infection was abolished and CD11a expression was partially reduced when mice were treated with drugs. T cells activated by Plasmodium berghei ANKA antigens showed 6-fold enhance in AT(1) levels in comparison with naive cells. The upregulation of AT(1) expression was reduced by losartan (80%) but not by captopril. Our results suggest that the AT(1)/Ang II axis has a role in the establishment of an efficient T cell response in the spleen and therefore could participate in a misbalanced parasite-induced T cell immune response during P. berghei ANKA infection.

• 出版日期2013-4-30