Herrera María Teresa, Gonzalez Yolanda, Hernández-Sánchez Fernando, Fabián-San Miguel Guadalupe, Torres Martha
Departamento de Investigación en Microbiología, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas", Calzada de Tlalpan 4502, 14080, Ciudad de México, Mexico.
Clínica del Síndrome Metabólico, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas", Calzada de Tlalpan 4502, 14080, Ciudad de México, Mexico.
BMC Infect Dis. 2017 Sep 7;17(1):610. doi: 10.1186/s12879-017-2705-1.
Concurrent diabetes mellitus and tuberculosis represent a significant health problem worldwide. Patients with diabetes mellitus have a high risk of tuberculosis, which may be mediated by an abnormal innate immune response due to hyperglycaemia or low vitamin D levels.
In the present study, we evaluated inactive vitamin D serum levels and the monocyte response to infection with M. tuberculosis, including phagocytosis of M. tuberculosis, antimycobacterial activity, LL-37, human β defensin-2 and IL-10 gene expression and nitric oxide production, between type 2 diabetes mellitus patients (n = 51) and healthy volunteers (n = 38).
Twenty-seven type 2 diabetes mellitus patients had inadequate inactive vitamin D levels (<50 nM). The percentages of M. tuberculosis phagocytosis between monocytes were similar across groups according to microscopy. Intracellular mycobacterial growth was similar in infected monocytes from both groups. However, M. tuberculosis growth was significantly higher in monocytes obtained from type 2 diabetes mellitus patients and lower vitamin D levels after 1-h (D0) and 72-h (D3) post-infection (p ≤ 0.05). LL-37, human β defensin-2 and IL-10 mRNA expression were similar between monocytes across groups; vitamin D serum levels and LL-37, human β defensin-2 and IL-10 expression were not correlated. Nitric oxide production was significantly higher in healthy volunteers than in type 2 diabetes mellitus patients with low vitamin D serum levels at D3 post-infection (p ≤ 0.05).
Our results show that monocytes from type 2 diabetes mellitus patients and low vitamin D serum levels show an impaired ability to control the intracellular growth of M. tuberculosis, which is not associated with significant decrease of LL-37 or human β defensin-2 expression. Vitamin D could be the link between diabetes and tuberculosis susceptibility.
糖尿病与结核病并存是全球一个重大的健康问题。糖尿病患者患结核病的风险很高，这可能是由高血糖或低维生素D水平导致的异常先天免疫反应介导的。
在本研究中，我们评估了2型糖尿病患者（n = 51）和健康志愿者（n = 38）中维生素D非活性血清水平以及单核细胞对结核分枝杆菌感染的反应，包括结核分枝杆菌的吞噬作用、抗分枝杆菌活性、LL-37、人β防御素-2和IL-10基因表达以及一氧化氮生成。
27例2型糖尿病患者维生素D非活性水平不足（<50 nM）。根据显微镜检查，各组单核细胞中结核分枝杆菌的吞噬百分比相似。两组受感染单核细胞内的分枝杆菌生长情况相似。然而，在感染后1小时（D0）和72小时（D3），从2型糖尿病患者获得的单核细胞中结核分枝杆菌的生长明显更高，且维生素D水平较低（p≤0.05）。各组单核细胞之间LL-37、人β防御素-2和IL-10 mRNA表达相似；维生素D血清水平与LL-37、人β防御素-2和IL-10表达无相关性。在感染后D3时，健康志愿者的一氧化氮生成明显高于维生素D血清水平低的2型糖尿病患者（p≤0.05）。
我们的结果表明，2型糖尿病患者且维生素D血清水平低的单核细胞控制结核分枝杆菌细胞内生长的能力受损，这与LL-37或人β防御素-2表达的显著降低无关。维生素D可能是糖尿病与结核病易感性之间的联系。
