title: Angiotensin II is a new component involved in splenic T lymphocyte responses during Plasmodium berghei ANKA infection.
abstract: 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 AT₁ receptor antagonist, or captopril (IC₅₀ = 1.940 mg/kg/d), an inhibitor of angiotensin-converting enzyme (ACE). Moreover, the production of interferon-γ 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 AT₁ levels in comparison with naive cells. The upregulation of AT₁ expression was reduced by losartan (80%) but not by captopril. Our results suggest that the AT₁/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.
authors: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors: João Luiz
authors: JL
authors: Silva-Filho
authors: Mariana Conceição
authors: MC
authors: Souza
authors: Claudio Teixeira
authors: CT
authors: Ferreira-Dasilva
authors: Leandro Souza
authors: LS
authors: Silva
authors: Maria Fernanda Souza
authors: MF
authors: Costa
authors: Tatiana Almeida
authors: TA
authors: Padua
authors: Maria das Graças
authors: Md
authors: Henriques
authors: Alexandre
authors: A
authors: Morrot
authors: Wilson
authors: W
authors: Savino
authors: Celso
authors: C
authors: Caruso-Neves
authors: Ana Acacia Sá
authors: AA
authors: Pinheiro
mesh_terms: D000804:Angiotensin II / Q000276:immunology / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000097:blood; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008288:Malaria / Q000276:immunology* / Q000378:metabolism*; D016779:Malaria, Cerebral / Q000276:immunology; D051379:Mice; D010962:Plasmodium berghei / Q000276:immunology*; D013154:Spleen / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D016207:Cytokines; D018836:Inflammation Mediators; D000804:Angiotensin II
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