Eukaryotic and prokaryotic chaperonin 60s (Cpn60s) activate macrophages to produce pro-inflammatory cytokines. CD14 and TLR4 have been proposed as potential Cpn receptors. In addition, Cpn60s can block LPS-induced activation. This is a dose-related effect, low concentrations block, and high concentrations activate. This may relate to the ability of Cpn60s to block inflammatory disease. Cpns are multiplex or moon-lighting proteins, with functions as molecular chaperones, in stress survival and as inflammatory modulators. A cpn60.1 knockout mutant does not induce a granulomatous response and cytokine levels, such as tumour necrosis factor are reduced in the tissues. These data suggest that Cpn60.1 may also function as a virulence factor.