Failure to detect production of IL-10 by activated human neutrophils

MS Davey, N Tamassia, M Rossato, F Bazzoni… - Nature …, 2011 - nature.com
MS Davey, N Tamassia, M Rossato, F Bazzoni, F Calzetti, K Bruderek, M Sironi, L Zimmer…
Nature immunology, 2011nature.com
We read with great interest the paper by De Santo et al. 1 published in the November 2010
issue of Nature Immunology, which has received wide attention because of its potential
implications for inflammation and immunotherapy. The authors show that the acute-phase
protein serum amyloid A1 (SAA-1) induces substantial secretion of the immunosuppressive
cytokine interleukin 10 (IL-10) by human neutrophils (up to 100–400 ng/ml) and that
invariant natural killer T cells (iNKT cells) are able to diminish this. The authors conclude that …
We read with great interest the paper by De Santo et al. 1 published in the November 2010 issue of Nature Immunology, which has received wide attention because of its potential implications for inflammation and immunotherapy. The authors show that the acute-phase protein serum amyloid A1 (SAA-1) induces substantial secretion of the immunosuppressive cytokine interleukin 10 (IL-10) by human neutrophils (up to 100–400 ng/ml) and that invariant natural killer T cells (iNKT cells) are able to diminish this. The authors conclude that harnessing iNKT cells might “be useful therapeutically by decreasing the frequency of immunosuppressive neutrophils and restoring tumor-specific immune responses” in patients with melanoma and other patients with high plasma SAA-1 concentrations1.
Intimate crosstalk of neutrophils and monocytes with another population of ‘unconventional’human T cells, Vγ9Vδ2+ γδ T cells, has been demonstrated2. Of relevance for immunotherapy, Vγ9Vδ2+ T cells are much more abundant in human blood than are iNKT cells and can readily be activated by aminobisphosphonate drugs such as zoledronate (Zometa). Small-scale trials have shown promising results for therapy targeting Vγ9Vδ2+ T cells to treat metastatic disease in patients with multiple myeloma, prostate cancer or breast cancer3. Thus, we were keen to ‘translate’the described interaction of iNKT cells with neutrophils to our own experimental system2, 4 and to test whether activated Vγ9Vδ2+ T cells likewise inhibits IL-10-producing neutrophils. Unexpectedly, we found that highly purified, obtained by negative selection human neutrophils (Supplementary Fig. 1) did not secrete IL-10 (Fig. 1a) or express IL-10 mRNA (Fig. 1b) in response to recombinant SAA-1 at the same concentrations used by De Santo et al. 1 Notably, and in contrast to De Santo et al., we also did not detect IL-10 in the culture supernatants of neutrophils stimulated with either
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