Legionella pneumophila Suppresses Interleukin-12 Production by Macrophages

In vitro infection of macrophages with Legionella pneumophila induced interleukin-1α (IL-1α), IL-10, monocyte chemotactic protein 1 (MCP-1), and MCP-3 but not IL-12. The lipopolysaccharide (LPS)-induced production of IL-12 was down-regulated by infection with virulent L. pneumophila, but other 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 accumulation of mRNA for both MCP-1 and MCP-3, which are known to suppress IL-12 production in LPS-stimulated macrophages. However, pretreatment of macrophages with MCP-1 did not suppress LPS-induced IL-12 production at the concentrations induced by L. pneumophila infection. These results suggest that L. pneumophila selectively suppresses IL-12 production induced by LPS from macrophages in vitro by an MCP-independent mechanism.

体外感染嗜肺军团菌（Legionella pneumophila）可诱导巨噬细胞产生白细胞介素1α（interleukin-1α，IL-1α）、白细胞介素10（interleukin-10，IL-10）、单核细胞趋化蛋白1（monocyte chemotactic protein 1，MCP-1）及单核细胞趋化蛋白3（MCP-3），但无法诱导白细胞介素12（interleukin-12，IL-12）的产生。脂多糖（lipopolysaccharide，LPS）诱导的IL-12产生可被毒力株嗜肺军团菌感染下调，但对其他细胞因子的表达无显著影响。与之相反，无毒株嗜肺军团菌或紫外线灭活的毒力株嗜肺军团菌均未对IL-12的产生产生抑制作用。IL-12的抑制作用发生在LPS刺激下IL-12基因的mRNA积累层面，而该感染可显著上调MCP-1与MCP-3的mRNA积累——已知这两种因子可抑制LPS刺激下巨噬细胞的IL-12产生。然而，以嗜肺军团菌感染所诱导的浓度的MCP-1预处理巨噬细胞，并未抑制LPS诱导的IL-12产生。上述结果表明，嗜肺军团菌可通过不依赖于MCP的机制，在体外选择性抑制巨噬细胞中LPS诱导的IL-12产生。