Captopril increases the intensity of monocyte infection by Trypanosoma cruzi and induces human T helper type 17 cells.
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2010
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The anti-hypertensive drug captopril is used commonly to reduce blood pressure
of patients with severe forms of Chagas disease, a cardiomyopathy caused
by chronic infection with the intracellular protozoan Trypanosoma cruzi.
Captopril acts by inhibiting angiotensin-converting enzyme (ACE), the vasopressor
metallopeptidase that generates angiotensin II and promotes the degradation
of bradykinin (BK). Recent studies in micemodels of Chagas disease
indicated that captopril can potentiate the T helper type 1 (Th1)-directing
natural adjuvant property of BK. Equipped with kinin-releasing cysteine proteases,
T. cruzi trypomastigotes were shown previously to invade nonprofessional
phagocytic cells, such as human endothelial cells and murine
cardiomyocytes, through the signalling of G protein-coupled bradykinin
receptors (B2KR). Monocytes are also parasitized by T. cruzi and these cells
are known to be important for the host immune response during infection.
Here we showed that captopril increases the intensity of T. cruzi infection of
human monocytes in vitro. The increased parasitism was accompanied by
up-regulated expression of ACE in human monocytes.While T. cruzi infection
increased the expression of interleukin (IL)-10 by monocytes significantly,
compared to uninfected cells, T. cruzi infection in association with captopril
down-modulated IL-10 expression by the monocytes. Surprisingly, studies
with peripheral blood mononuclear cells revealed that addition of the ACE
inhibitor in association with T. cruzi increased expression of IL-17 by CD4+ T
cells in a B2KR-dependent manner. Collectively, our results suggest that captopril
might interfere with host–parasite equilibrium by enhancing infection
of monocytes, decreasing the expression of the modulatory cytokine IL-10,
while guiding development of the proinflammatory Th17 subset.
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SANTOS. J. S. C. dos et al. Captopril increases the intensity of monocyte infection by Trypanosoma cruzi and induces human T helper type 17 cells. Clinical and Experimental Immunology, v. 162, p. 528-536, 2010. Disponível em: <http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2249.2010.04270.x/abstract>. Acesso em: 19 fev. 2017.