Cytokine release in healthy donors and patients with chronic granulomatous disease upon stimulation with Aspergillus fumigatus.
The release of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-10 upon stimulation with non-viable conidia and hyphal fragments from Aspergillus fumigatus was investigated in an ex vivo whole-blood model. In healthy volunteers, high numbers of conidia (between 10(6) and 3 x 10(8)/ml) induced a moderate release of TNF-alpha and IL-6. Hyphal fragments (2.5 x 10(5)/ml) were more potent in stimulating the release of these pro-inflammatory cytokines. Although some IL-10 release was observed upon stimulation with either conidia or hyphal fragments, it was not significantly different from that in unstimulated controls. In comparison, in whole blood obtained from 4 patients with chronic granulomatous disease (CGD), a high release of pro-inflammatory cytokines together with a significantly higher IL-10 release than in the healthy controls was seen after stimulation with A. fumigatus. In conclusion, A. fumigatus can trigger the release of pro-inflammatory cytokines in a human whole-blood system, which is likely to be central to the activation of antifungal defence mechanisms. In contrast, A. fumigatus stimulates a higher release of anti-inflammatory cytokines in CGD patients, which may suggest that a dysregulation between pro- and anti-inflammatory cytokines contributes to the increased susceptibility to invasive aspergillosis in this patient group.
D001232:Aspergillus fumigatus; D001782:Blood Donors; D016022:Case-Control Studies; D016207:Cytokines / Q000032:analysis / Q000097:blood; D006105:Granulomatous Disease, Chronic / Q000097:blood* / Q000628:therapy; D006801:Humans; D016753:Interleukin-10 / Q000032:analysis / Q000097:blood*; D015850:Interleukin-6 / Q000032:analysis / Q000097:blood*; D011336:Probability; D012016:Reference Values; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10