Legionella pneumophila suppresses interleukin-12 production by macrophages

In vitro infection of macrophages with Legionella pneumophila induced inter leukin-1 alpha (IL-1 alpha), IL-10, monocyte chemotactic protein 1 (MCP-1), and MCP-3 but not IL-12. The lipopolysaccharide (LPS)-induced production o f IL-12 was down-regulated by infection with virulent L. pneumophila, but o ther cytokines were not affected. In contrast, avirulent L. pneumophila or UV-killed, virulent L. pneumophila did not induce any suppression of IL-12. The IL-12 suppression occurred at the level of mRNA accumulation for IL-12 genes in response to LPS stimulation, but the infection induced a marked a ccumulation of mRNA for both MCP-1 and MCP-3, which are known to suppress I L-12 production in LPS-stimulated macrophages. However, pretreatment of mac rophages with MCP-1 did not suppress LPS-induced IL-12 production at the co ncentrations induced by L. pneumophila infection. These results suggest tha t L. pneumophila selectively suppresses IL-12 production induced by LPS fro m macrophages in vitro by an MCP-independent mechanism.