Abstract
BackgroundConcurrent 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.MethodsIn 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).ResultsTwenty-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).ConclusionsOur 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.
Highlights
Concurrent diabetes mellitus and tuberculosis represent a significant health problem worldwide
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
Our results showed that the percentages of monocytes that phagocytosed M. tuberculosis were similar (p>0.05) in type 2 diabetes mellitus (T2D) patients (Fig. 2a) and healthy volunteers (Fig. 2b), and phagocytosis was not associated with levels of vitamin D (Fig. 2c)
Summary
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. Vitamin D insufficiency is a risk factor for osteomalacia in adults and rickets in children and is associated with a variety of conditions, such as various cancers, type 1 and 2 diabetes, hypertension, multiple sclerosis, metabolic syndrome and infectious diseases, including tuberculosis [1,2,3,4]. The human body can synthesize vitamin D from the precursor molecule 7-dehydrocholesterol, which is generated by the skin upon sufficient exposure to solar ultraviolet radiation. Since the final effector molecule of vitamin D is produced in humans, vitamin D is considered a pro-hormone [5]. Vitamin D status is determined by measuring circulating 25-hydroxyvitamin D (25OHD3), which is the predominant inactive form in plasma or serum and is the first hydroxylation product of vitamin D that is synthesized in the liver.
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