Diesel exhaust particles modify natural killer cell function and cytokine release

Abstract

BackgroundNatural killer (NK) cells are an important lymphocyte population in the nasal mucosa and play important roles in linking the innate and the adaptive immune response. Their two main functions are direct cell-mediated cytotoxicity and the release of cytokines. They are important during viral infections and cancer. Due to their location in the nasal mucosa, NK cells are likely exposed to inhaled pollutants, such as diesel exhaust. Whether and how exposure to diesel exhaust particles (DEP) affects NK cell function in the context of viral infections has not been investigated.MethodsNK cells were isolated from peripheral blood obtained from normal healthy volunteers and subsequently stimulated with the viral mimetic polyinosinic:polycytidylic acid (pI:C), DEP, or pI:C+DEP for 18 hours. NK cells were subsequently analyzed for changes in surface marker expression, cytokine production, gene expression changes, and cytotoxic function using flow cytometry, ELISA, qRT-PCR, and cell-mediated cytotoxicity assay, respectively.ResultsStimulation of NK cells with pI:C and pI:C+DEP, but not DEP alone, increased the release of IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12p70, IFN-γ and TNF-α. As compared to pI:C alone or pI:C+DEP, the release of IL-1β, IL-8 and TNF-α was significantly lower after DEP stimulation alone. Stimulation with pI:C alone increased the gene and protein expression of granzyme B and perforin, which was completely blunted by adding DEP. Addition of DEP further reduced CD16 expression in pI:C stimulated cells. Similarly, cell-mediated cytotoxicity was significantly reduced by the addition of DEP.ConclusionsIn the context of viral infection, DEP potentially reduces NK cells' ability to kill virus-infected host cells, in spite of normal cytokine levels, and this may increase susceptibility to viral infections . This reduction in the potential ability of NK cells to kill virus-infected host cells may increase the susceptibility to viral infections after DEP exposure.

Analysis of sphingosine kinase activity in single natural killer cells from peripheral blood

“…29-31 The cells were fixed in 0.5% paraformaldehyde, and analyzed within 24 hours of fixation by flow cytometer (BD LSRII, BD Biosciences). Data were analyzed with FLOWJO (TreeStar, Ashland, OR).…”

Vanadium pentoxide increased PTEN and decreased SHP1 expression in NK-92MI cells, affecting PI3K-AKT-mTOR and Ras-MAPK pathways

“…Mice and humans exposed to pollutants derived from burning coal or diesel exhaust particles show a diminished NK cell function (Hurd and Whalen 2011;Dutta et al 2012;Wortham et al 2012;Muller et al 2013). Interleukin (IL)-2, a cytokine required for NK cell proliferation and activation (Suzuki et al 1983;Bi et al 2014;Leon et al 2014) has its effects mediated through IL-2 receptors and subsequently janus kinase/signal transducers and activators of transcription (JAK/STAT), phosphoinositide 3-kinase-protein kinase B-mechanistic target of Rapamycin (PI3K-Akt-mTOR) and mitogen-activated protein kinase (MAPK) signaling pathways (Lu et al 1998;Liao et al 2013).…”

Public health and components of particulate matter: The changing assessment of black carbon

“…One result could be increased prevalence of infectious pulmonary disease. For example, DPM was found to suppress cell-mediated cytotoxicity by affecting the activity of natural killer (NK) cells (Muller et al, 2013), which may result in a reduced ability to kill virus-infected cells, thus increasing susceptibility to viral infection. Increased viral susceptibility in DEE-exposed animals has been reported (McDonald et al, 2004.…”