1.
Toll-like receptor 8 agonist and bacteria trigger potent activation of innate immune cells in human liver.
Jo, J, Tan, AT, Ussher, JE, Sandalova, E, Tang, XZ, Tan-Garcia, A, To, N, Hong, M, Chia, A, Gill, US, et al
PLoS pathogens. 2014;(6):e1004210
Abstract
The ability of innate immune cells to sense and respond to impending danger varies by anatomical location. The liver is considered tolerogenic but is still capable of mounting a successful immune response to clear various infections. To understand whether hepatic immune cells tune their response to different infectious challenges, we probed mononuclear cells purified from human healthy and diseased livers with distinct pathogen-associated molecules. We discovered that only the TLR8 agonist ssRNA40 selectively activated liver-resident innate immune cells to produce substantial quantities of IFN-γ. We identified CD161(Bright) mucosal-associated invariant T (MAIT) and CD56(Bright) NK cells as the responding liver-resident innate immune cells. Their activation was not directly induced by the TLR8 agonist but was dependent on IL-12 and IL-18 production by ssRNA40-activated intrahepatic monocytes. Importantly, the ssRNA40-induced cytokine-dependent activation of MAIT cells mirrored responses induced by bacteria, i.e., generating a selective production of high levels of IFN-γ, without the concomitant production of TNF-α or IL-17A. The intrahepatic IFN-γ production could be detected not only in healthy livers, but also in HBV- or HCV-infected livers. In conclusion, the human liver harbors a network of immune cells able to modulate their immunological responses to different pathogen-associated molecules. Their ability to generate a strong production of IFN-γ upon stimulation with TLR8 agonist opens new therapeutic opportunities for the treatment of diverse liver pathologies.
2.
Oral supplementation with 25(OH)D3 versus vitamin D3: effects on 25(OH)D levels, lower extremity function, blood pressure, and markers of innate immunity.
Bischoff-Ferrari, HA, Dawson-Hughes, B, Stöcklin, E, Sidelnikov, E, Willett, WC, Edel, JO, Stähelin, HB, Wolfram, S, Jetter, A, Schwager, J, et al
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2012;(1):160-9
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Abstract
To test the effect of 25(OH)D(3) (HyD) compared to vitamin D(3) on serum 25-hydroxyvitamin D levels (25(OH)D), lower extremity function, blood pressure, and markers of innate immunity. Twenty healthy postmenopausal women with an average 25(OH)D level of 13.2 ± 3.9 ng/mL (mean ± SD) and a mean age of 61.5 ± 7.2 years were randomized to either 20 µg of HyD or 20 µg (800 IU) of vitamin D(3) per day in a double-blind manner. We measured on 14 visits over 4 months, 25(OH)D serum levels, blood pressure, and seven markers of innate immunity (eotaxin, interleukin [IL]-8, IL-12, interferon gamma-induced protein 10 kDa [IP-10], monocyte chemotactic protein-1 [MCP-1], macrophage inflammatory protein beta [MIP-1β], and "Regulated upon Activation, Normal T-cell Expressed, and Secreted" [RANTES]). At baseline and at 4 months, a test battery for lower extremity function (knee extensor and flexor strength, timed up and go, repeated sit-to-stand) was assessed. All analyses were adjusted for baseline measurement, age, and body mass index. Mean 25(OH)D levels increased to 69.5 ng/mL in the HyD group. This rise was immediate and sustained. Mean 25(OH)D levels increased to 31.0 ng/mL with a slow increase in the vitamin D(3) group. Women on HyD compared with vitamin D(3) had a 2.8-fold increased odds of maintained or improved lower extremity function (odds ratio [OR] = 2.79; 95% confidence interval [CI], 1.18-6.58), and a 5.7-mmHg decrease in systolic blood pressure (p = 0.0002). Both types of vitamin D contributed to a decrease in five out of seven markers of innate immunity, significantly more pronounced with HyD for eotaxin, IL-12, MCP-1, and MIP-1 β. There were no cases of hypercalcemia at any time point. Twenty micrograms (20 µg) of HyD per day resulted in a safe, immediate, and sustained increase in 25(OH)D serum levels in all participants, which may explain its significant benefit on lower extremity function, systolic blood pressure, and innate immune response compared with vitamin D(3).
3.
Breast feeding and childhood hematological malignancy.
Tripathy, AK, Mishra, L, Bakhshi, S, Arya, LS
Indian journal of pediatrics. 2004;(5):417-8
Abstract
Breast milk is known to have anti-infective and immunomodulating effects on infants, but its association with childhood cancer has not been well studied. Artificial feeding may affect the immune response in carcinogenesis. In this communication the authors have reviewed different articles describing the association between breast feeding (BF) and subsequent development of childhood hematological malignancy. It appears that BF may have a protective effect on childhood cancer, both the duration of BF as well as the quantity of milk ingested is probably critical to the beneficial immunological effects of BF against childhood cancer if any.