Silicosis (via OSHA)

A couple of years ago1 it was discovered that the natural adjuvant uric acid stimulates immunity through an intracellular sensor called the Nalp3 inflammasome.  Last year, a bunch of groups showed the the commonly-used adjuvant alum — also kind of crystalline — acts through the Nalp3 inflammasome. 2  Then it turned out that silca causes the inflammation associated with silicosis via, right, the Nalp3 inflammasome. 3 (I talked about this in several places, including here.)

So it wasn’t a stretch to wonder if perhaps this was a general rule, and all (or at least most) particulate-type adjuvants act through the Nalp3 inflammasome.  And unsurprisingly, this turns out to be the case:

The ability of alum to enhance IL-1β secretion via NALP3 has been described, but our data indicate that this is not specific to alum but is a general property of all particulate adjuvants. 4

Not really a shock, I guess, at this point; but it’s nice to see things fitting neatly into a general model for a change.

  1. Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. 440, 237 – 241 (11 Jan 2006), doi:10.1038/nature04516[]
  2. Eisenbarth SC, Colegio OR, O’Connor W, Sutterwala FS, Flavell RA (2008) Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature  453, 1122-1126 doi:10.1038/nature06939

    Cutting edge: alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome. Kool M, Pétrilli V, De Smedt T, Rolaz A, Hammad H, van Nimwegen M, Bergen IM, Castillo R, Lambrecht BN, Tschopp J.J Immunol. 2008 Sep 15;181(6):3755-9.

    The Nlrp3 inflammasome is critical for aluminium hydroxide-mediated IL-1beta secretion but dispensable for adjuvant activity. Franchi L, Núñez G.  Eur J Immunol. 2008 Aug;38(8):2085-9.[]

  3. Cassel, S.L., Eisenbarth, S.C., Iyer, S.S., Sadler, J.J., Colegio, O.R., Tephly, L.A., Carter, A.B., Rothman, P.B., Flavell, R.A., Sutterwala, F.S. (2008). The Nalp3 inflammasome is essential for the development of silicosis. Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0803933105[]
  4. F. A. Sharp, D. Ruane, B. Claass, E. Creagh, J. Harris, P. Malyala, M. Singh, D. T. O’Hagan, V. Petrilli, J. Tschopp, L. A. J. O’Neill, E. C. Lavelle (2009). Uptake of particulate vaccine adjuvants by dendritic cells activates the NALP3 inflammasome Proceedings of the National Academy of Sciences, 106 (3), 870-875 DOI: 10.1073/pnas.0804897106[]