Impact of Aging and HIV Infection on the Function of the C-Type Lectin Receptor MINCLE in Monocytes

AbstractBoth aging and HIV infection are associated with an enhanced pro-inflammatory environment that contributes to impaired immune responses and is mediated in part by innate immune pattern-recognition receptors. MINCLE is a C-type lectin receptor that recognizes trehalose-6,6ʹ-dimycolate or “cord factor,” the most abundant glycolipid in Mycobacterium tuberculosis. Here, we evaluated MINCLE function in monocytes in a cohort of HIV-infected and uninfected young (21–35 years) and older adults (≥60 years) via stimulation of peripheral blood mononuclear cells with trehalose-6,6-dibehenate, a synthetic analog of trehalose-6,6ʹ-dimycolate and measurement of cytokine production (interleukin [IL]-10, IL-12, IL-6, tumor necrosis factor-α) by multicolor flow cytometry. Our studies show an age- and HIV-associated increase in cytokine multifunctionality of monocytes both at the population and single cell level that was dominated by IL-12, IL-10, and IL-6. These findings provide insight into the host response to M. tuberculosis and possible sources for the pro-inflammatory environment seen in aging and HIV infection.

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Exposing endothelial cells to tumor necrosis factor-α and peripheral blood mononuclear cells damage endothelial integrity via interleukin-1ß by degradation of vascular endothelial-cadherin

Surgery ◽

10.1016/j.surg.2013.10.019 ◽

2014 ◽

Vol 155 (3) ◽

pp. 545-553 ◽

Cited By ~ 6

Author(s):

Ann L.B. Seynhaeve ◽

Joost A.P. Rens ◽

Debby Schipper ◽

Alexander M.M. Eggermont ◽

Timo L.M. ten Hagen

Keyword(s):

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Mononuclear Cells ◽

Vascular Endothelial ◽

Peripheral Blood Mononuclear ◽

Vascular Endothelial Cadherin ◽

Blood Mononuclear Cells ◽

Factor Α ◽

Endothelial Integrity ◽

Necrosis Factor

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Effect of soluble interleukin-6 receptor α and interleukin-6 secreted by polymorphonuclear leukocytes on tumor necrosis factor-α expression and its production by peripheral blood mononuclear cells

Mediators of Inflammation ◽

10.1080/09629350210000015746 ◽

2002 ◽

Vol 11 (5) ◽

pp. 325-328 ◽

Cited By ~ 2

Author(s):

E. Jablonska

Keyword(s):

Interleukin 6 ◽

Polymorphonuclear Leukocytes ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Tnf Α ◽

Interleukin 6 Receptor ◽

Factor Α ◽

Necrosis Factor

Background: It has recently been shown that soluble interleukin-6 receptor (sIL-6R) alone or complexed with interleukin (IL)-6, besides their regulatory role in a wide variety of both normal and abnormal biologic reactions mediated by IL-6, could be an effective stimulator of the cell function.Aims: The key question of the present study is whether the sIL-6Rα or sIL-6R with IL-6 released by polymorphonuclear leukocytes (PMN) can influence cytokine secretion such as tumor necrosis factor-α (TNF-α) by peripheral blood mononuclear cells (PBMC), which together with PMN develop the inflammatory and immune response of a host.Methods: Cells were isolated from heparinized whole blood of healthy persons. The PMN were cultured for 1 h at 37°C in 5% CO2. After incubation, the culture supernatant of PMN was removed and was added to PBMC. The PBMC were cultured for 1 h at 37°C in the same conditions. In the culture supernatants and lysates of PMN, we examined the concentrations of sIL-6R by enzyme-linked immunosorbent assay (ELISA). TNF-α was measured at both protein and mRNA levels. Protein levels were determined by ELISA. To examine TNF-α mRNA expression, we isolated mRNA from PBMC after culture, using TRIZOL Reagent. The quantity of mRNA TNF-α was determined by the Quantikine mRNA assay.Results and conclusion: The results obtained revealed that sIL-6R with IL-6 secreted by PMN may play a regulatory role in the immune response by modulating the TNF-α expression and its production by PBMC. This may have a significant influence on an early phase of the inflammation and other reactions mediated by TNF-α.

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