Serum and brain purine levels in an experimental systemic infection of mice by Cryptococcus neoformans: Purinergic immunomodulatory effects

被引:2
|
作者
de Azevedo, Maria Isabel [1 ,2 ]
Da Silva, Aleksandro S. [3 ]
Ferreiro, Laerte [1 ]
Doleski, Pedro H. [2 ]
Tonin, Alexandre A. [2 ]
Casali, Emerson A. [4 ,5 ,6 ]
Moritz, Cesar E. J. [7 ]
Schirmbeck, Gabriel H. [4 ]
Cardoso, Valesca V. [6 ]
Flores, Mariana M. [8 ]
Fighera, Rafael [8 ]
Santurio, Janio M. [2 ]
机构
[1] Univ Fed Rio Grande do Sul, Dept Patol & Clin Anim, Porto Alegre, RS, Brazil
[2] Univ Fed Santa Maria, Dept Microbiol & Parasitol, Santa Maria, RS, Brazil
[3] Univ Estado Santa Catarina, Dept Zootecnia, Chapeco, SC, Brazil
[4] Univ Fed Rio Grande do Sul, ICBS, Dept Ciencias Morfol, Porto Alegre, RS, Brazil
[5] Univ Fed Rio Grande do Sul, ICBS, Dept Bioquim, Porto Alegre, RS, Brazil
[6] Ctr Univ Metodista IPA, Lab Mutagenese & Toxicol, Porto Alegre, RS, Brazil
[7] UFGRS, Escola Educ Fis Fisioterapia & Danca, Programa Posgrad Ciencias Movitnento Humano, Porto Alegre, RS, Brazil
[8] Univ Fed Santa Maria, Dept Patol, Santa Maria, RS, Brazil
关键词
Cryptococcosis; Purinergic system; Neurotransmitter; Neuromodulator; Pathogenesis; ADENOSINE; METABOLISM; IMMUNITY; ATP;
D O I
10.1016/j.micpath.2017.10.012
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The aim of this study was to evaluate the purine levels in serum and brains of mice experimentally infected by Cryptococcus neoformans. Twenty-four mice were divided into the following groups: a control group (n = 12; Group A) and an infection group with animals that were infected (n = 12; Group B) with a 0.3-mL intraperitoneal injection containing 1.7 x 10(7) C. neoformans cells. Blood and brains were collected on days 20 (n = 6 per group) and 50 (n = 6 per group) post-infection (PI). Histopathology and lung and brain cultures were performed to confirm fungal infection and tissue injuries. The levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), adenosine (ADO), inosine (INO), hypoxanthine (HYPO), xanthine (XAN) and uric acid (UA) in brains and serum were measured by high-performance liquid chromatography (HPLC) analysis. At both time points, histopathology analysis revealed inflammatory infiltrates in the brains and lungs of infected mice; clinical signs, such as piloerection and clinical respiratory distress, were also observed. ATP levels were significantly increased on days 20 and 50 PI (P < 0.01) in brains and serum, while brain ADO levels were increased on day 20 PI; brain and serum ADO levels were decreased on day 50 PI. Levels of ADP and AMP did not differ between groups (P > 0.05). Serum levels of INO of infected mice increased only on day 50 PI (P < 0.05). HYPO levels were reduced in the brains of infected animals at both experimental time points and were decreased in serum at day 50 PI (P < 0.05). XAN levels increased in infected mice only in serum on day 50 PI (P < 0.05). The endogenous anti-oxidant uric acid was significantly increased in brain (days 20 and 50 PI) and decreased in serum. It is possible that C. neoformans infection in mice leads to a high ATP/ADO ratio that may improve the brain pro-inflammatory response during both periods, while high ATP levels in serum act as a systemic signal to improve the immune response. Moreover, the anti-oxidant uric acid may increase in the brain to protect inflamed tissue from oxidative stress.
引用
收藏
页码:124 / 128
页数:5
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