Avaliação do papel das citocinas interleucina 32 e interleucina 15 em macrófagos humanos primários infectados com Leishmania (Viannia) braziliensis
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2016-05-13
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Universidade Federal de Goiás
Resumo
American Tegumentary Leishmaniasis (ATL) is a disease caused by Leishmania
protozoan, belonging to the subgenus Viannia and Leishmania. In Brazil, the most
common and prevalent species is L. (V.) braziliensis. In patients with ATL, it was detected
the expression of interleukin 32 (IL-32) in skin or mucosal lesions caused by L. Viannia
spp. However, the role of IL-32 on ATL is still unclear. It has been shown that IL-15
induces IL-32 and also IL-15 leads to L. infantum control. This study aimed to investigate
the effects of IL-32 and IL-15 in the production of cytokines and microbicidal activity of
primary human macrophages infected with L. (V.) braziliensis. For this, human peripheral
blood monocytes were derived into macrophages and infected with metacyclic forms of L.
(V.) braziliensis; evaluation of the infection index (4 h, phagocytosis, 48 h, microbicidal
activity) in the absence or presence of rIL-32, rIL-15 or gamma interferon (rIFN) and
lipopolysaccharide (LPS); in culture supernatants, IL-32, tumor necrosis factor (TNF) and
IL-10 were measured by enzime-linked immunoassay. The addition of rIL-32 to
macrophages did not significantly altered phagocytosis of the parasites or microbicidal
activity of macrophages. Classical activation of macrophages with rIFN plus LPS
decreased the infection index. rIL-32 em high concentration (200 ng/mL) was able to
induce TNF in uninfected or infected macrophages, and IL-10 was not induced. Parasites
induced lower amounts of intracellular IL-32 as well as rIFN0.1 ng / ml), but there was a
synergism between the activation signals provided by the parasites and rIFN (0.1 ng /
ml). In the opposite, rIFN in higher concentration (10 ng/mL) induced higher amounts of
IL-32, but its activity was partially inhibited by parasites. The rIL-15 was able to induce IL-
32 and TNF in macrophages, but not IL-10 in both non-infected or infected macrophages.
The rIL-15 also decreased phagocytosis of parasites by macrophages and increased the
microbicidal activity of these cells. The data suggest that IL-15 induces IL-32 and TNF
which can contribute to control of the infection. To evaluate the leishmanicidal mechanism
pathways induced by IL-15 and IL-32 can help in the development of new therapies for
the control of ATL.
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Silva, L.L.L. Avaliação do papel das citocinas interleucina 32 e interleucina 15 em macrófagos humanos primários infectados com Leishmania (Viannia) braziliensis. 2016. 94 f. Dissertação (mestrado em Biologia das Interações Parasito-Hospedeiro) - Universidade Federal de Goiás, Goiânia, 2016.